A method for determining the fraction of fetal nucleic acids in a maternal blood sample obtained from a pregnant woman comprising a mixture of fetal and maternal genomic DNA, wherein said fetal and maternal genomic DNA is cell-free DNA (cfDNA), said method comprising: (a) amplifying a plurality of polymorphic target nucleic acids in said mixture, wherein each of said plurality of polymorphic target nucleic acids comprises at least one single nucleotide polymorphism (SNP), and wherein each polymorphic target nucleic acid comprises at least one polymorphic site that differs from that present on another polymorphic target nucleic acid to generate a panel of polymorphic sites that contain a sufficient number of polymorphic sites of which at least 1 are informative; (b) performing massively parallel sequencing of at least a portion of the amplified product obtained in (a), wherein said sequencing comprises providing a plurality of sequence tags; and (c) based on said sequencing, determining said fraction of fetal nucleic acids, by using said plurality of sequence tags to: (i) identify at least one informative polymorphic site in said amplified polymorphic target nucleic acids, wherein said at least one informative polymorphic site is identified by the difference in the allelic sequences at each polymorphic site and the number of sequence tags mapped to each of the possible alleles at each polymorphic site, and (ii) determine said fraction of fetal nucleic acids by using the total number of tags that map to a first allele at an identified informative polymorphic site and the total number of tags that map to a second allele at the identified informative polymorphic site to calculate said fraction of fetal nucleic acids. (a) amplifying a plurality of polymorphic target nucleic acids in said mixture, wherein each of said plurality of polymorphic target nucleic acids comprises at least one single nucleotide polymorphism (SNP), and wherein each polymorphic target nucleic acid comprises at least one polymorphic site that differs from that present on another polymorphic target nucleic acid to generate a panel of polymorphic sites that contain a sufficient number of polymorphic sites of which at least 1 are informative; (b) performing massively parallel sequencing of at least a portion of the amplified product obtained in (a), wherein said sequencing comprises providing a plurality of sequence tags; and (c) based on said sequencing, determining said fraction of fetal nucleic acids, by using said plurality of sequence tags to: (i) identify at least one informative polymorphic site in said amplified polymorphic target nucleic acids, wherein said at least one informative polymorphic site is identified by the difference in the allelic sequences at each polymorphic site and the number of sequence tags mapped to each of the possible alleles at each polymorphic site, and (ii) determine said fraction of fetal nucleic acids by using the total number of tags that map to a first allele at an identified informative polymorphic site and the total number of tags that map to a second allele at the identified informative polymorphic site to calculate said fraction of fetal nucleic acids. (i) identify at least one informative polymorphic site in said amplified polymorphic target nucleic acids, wherein said at least one informative polymorphic site is identified by the difference in the allelic sequences at each polymorphic site and the number of sequence tags mapped to each of the possible alleles at each polymorphic site, and (ii) determine said fraction of fetal nucleic acids by using the total number of tags that map to a first allele at an identified informative polymorphic site and the total number of tags that map to a second allele at the identified informative polymorphic site to calculate said fraction of fetal nucleic acids. <EOS>