A computer-implemented method of determining a genotype of a fetus of a pregnant female at a first locus, the fetus having a mother being the pregnant female, wherein the mother is heterozygous at the first locus for a first allele and a second allele that is different from the first allele, the method comprising: receiving data from a plurality of reactions involving cell-free DNA molecules from a biological sample of the mother, wherein the biological sample is maternal plasma or serum and includes cell-free DNA molecules from the female subject and from the fetus, wherein each reaction indicates a presence or absence of the first allele and of the second allele, and wherein the data includes: a first set of quantitative data indicating a first amount of reactions that are positive for the presence of the first allele from the female subject and the fetus in the plurality of reactions; and a second set of quantitative data indicating a second amount of reactions that are positive for the presence of the second allele from the female subject and the fetus in the plurality of reactions; determining a parameter from the two data sets, wherein the parameter includes a ratio between the first amount and the second amount; comparing the parameter to one or more cutoff values to determine the genotype of the fetus, wherein the fetus is determined to only have the first allele at the first locus when the first amount is larger than the second amount by a degree specified by one of the one or more cutoff values, wherein the fetus is determined to only have the second allele at the first locus when the second amount is larger than the first amount by a degree specified by one of the one or more cutoff values, and wherein the fetus is determined to be heterozygous for the first allele and the second allele when the first amount and the second amount are statistically equal as specified by the one or more cutoff values. receiving data from a plurality of reactions involving cell-free DNA molecules from a biological sample of the mother, wherein the biological sample is maternal plasma or serum and includes cell-free DNA molecules from the female subject and from the fetus, wherein each reaction indicates a presence or absence of the first allele and of the second allele, and wherein the data includes: a first set of quantitative data indicating a first amount of reactions that are positive for the presence of the first allele from the female subject and the fetus in the plurality of reactions; and a second set of quantitative data indicating a second amount of reactions that are positive for the presence of the second allele from the female subject and the fetus in the plurality of reactions; a first set of quantitative data indicating a first amount of reactions that are positive for the presence of the first allele from the female subject and the fetus in the plurality of reactions; and a second set of quantitative data indicating a second amount of reactions that are positive for the presence of the second allele from the female subject and the fetus in the plurality of reactions; determining a parameter from the two data sets, wherein the parameter includes a ratio between the first amount and the second amount; comparing the parameter to one or more cutoff values to determine the genotype of the fetus, wherein the fetus is determined to only have the first allele at the first locus when the first amount is larger than the second amount by a degree specified by one of the one or more cutoff values, wherein the fetus is determined to only have the second allele at the first locus when the second amount is larger than the first amount by a degree specified by one of the one or more cutoff values, and wherein the fetus is determined to be heterozygous for the first allele and the second allele when the first amount and the second amount are statistically equal as specified by the one or more cutoff values.