A single assay method for detection of the presence or absence of copy number variation (CNV) of a genomic region in a mixed sample using a single assay, wherein the mixed sample is from any maternal fluid which comprises both maternal and fetal cell free nucleic acids, the assay method comprising the steps of: introducing a first set of fixed sequence oligonucleotides to a mixed sample under conditions that allow the fixed sequence oligonucleotides to specifically hybridize to complementary regions on 24 or more loci on a first chromosome, wherein at least one of the fixed sequence oligonucleotides comprises 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 on a second chromosome, wherein at least one of the fixed sequence oligonucleotides comprises universal primer regions; introducing one or more bridging oligonucleotides under conditions that allow the bridging oligonucleotides to specifically hybridize to regions in the loci between the regions complementary to the fixed sequence oligonucleotides of the sets; ligating the hybridized oligonucleotides to create contiguous ligation products complementary to the loci from the first chromosome and the loci from the second chromosome; 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 the loci from the first and second chromosomes in the mixed sample. introducing a first set of fixed sequence oligonucleotides to a mixed sample under conditions that allow the fixed sequence oligonucleotides to specifically hybridize to complementary regions on 24 or more loci on a first chromosome, wherein at least one of the fixed sequence oligonucleotides comprises 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 on a second chromosome, wherein at least one of the fixed sequence oligonucleotides comprises universal primer regions; introducing one or more bridging oligonucleotides under conditions that allow the bridging oligonucleotides to specifically hybridize to regions in the loci between the regions complementary to the fixed sequence oligonucleotides of the sets; ligating the hybridized oligonucleotides to create contiguous ligation products complementary to the loci from the first chromosome and the loci from the second chromosome; 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 the loci from the first and second chromosomes in the mixed sample. <EOS>