A single assay method for detection of the presence or absence of copy number variation of a genomic region and presence or absence of one or more polymorphisms in a mixed sample using a single assay, wherein the mixed sample comprises both maternal and fetal cell free nucleic acids and wherein the mixed sample is maternal plasma or maternal serum; the assay method comprising the steps of: introducing a first set of fixed sequence oligonucleotides to the mixed sample under conditions that allow the fixed sequence oligonucleotides to specifically hybridize to complementary regions on 24 or more loci in or associated with a first chromosome, wherein at least one of the fixed sequence oligonucleotides comprise universal primer regions; introducing a second set of fixed sequence oligonucleotides to the mixed sample under conditions that allow the fixed sequence oligonucleotides to specifically hybridize to complementary regions on 24 or more loci in or associated with a second chromosome, wherein at least one of the fixed sequence oligonucleotides comprise universal primer regions; introducing a third set of fixed sequence oligonucleotides to the mixed sample under conditions that allow the fixed sequence oligonucleotides to specifically hybridize to complementary regions on 24 or more loci with a putative polymorphism, wherein at least one of the fixed sequence oligonucleotides comprise universal primer regions; ligating the hybridized oligonucleotides to create contiguous ligation products complementary to the loci from the first chromosome, the loci from the second chromosome, and the loci with a putative polymorphism; amplifying the contiguous ligation products using the universal primer regions to create amplification products; and detecting and quantifying the amplification products by high throughput sequencing, wherein the selected loci are each measured on average at least 100 times; wherein detection of the amplification products correlates to the copy number of one or more genomic regions and the presence or absence of a polymorphism in one or more loci in the mixed sample. introducing a first set of fixed sequence oligonucleotides to the mixed sample under conditions that allow the fixed sequence oligonucleotides to specifically hybridize to complementary regions on 24 or more loci in or associated with a first chromosome, wherein at least one of the fixed sequence oligonucleotides comprise universal primer regions; introducing a second set of fixed sequence oligonucleotides to the mixed sample under conditions that allow the fixed sequence oligonucleotides to specifically hybridize to complementary regions on 24 or more loci in or associated with a second chromosome, wherein at least one of the fixed sequence oligonucleotides comprise universal primer regions; introducing a third set of fixed sequence oligonucleotides to the mixed sample under conditions that allow the fixed sequence oligonucleotides to specifically hybridize to complementary regions on 24 or more loci with a putative polymorphism, wherein at least one of the fixed sequence oligonucleotides comprise universal primer regions; ligating the hybridized oligonucleotides to create contiguous ligation products complementary to the loci from the first chromosome, the loci from the second chromosome, and the loci with a putative polymorphism; amplifying the contiguous ligation products using the universal primer regions to create amplification products; and detecting and quantifying the amplification products by high throughput sequencing, wherein the selected loci are each measured on average at least 100 times; wherein detection of the amplification products correlates to the copy number of one or more genomic regions and the presence or absence of a polymorphism in one or more loci in the mixed sample.