A method of characterizing a sample comprising polynucleotide sequences, the method comprising: labeling a plurality of sample nucleic acid molecules, each of 500 base pairs or less, with at least a first label, wherein the sample molecules comprise polynucleotide sequences of a genomic fragment or fragments of interest, wherein the sample is derived from maternal blood, and wherein the reference molecules are derived from a maternal sample other than blood, and wherein the genomic fragment or fragments of interest correspond to a possibly abnormal genomic region; providing a plurality of labeled reference nucleic acid molecules, each of 500 base pairs or less, wherein the reference molecules comprise polynucleotide sequences of a reference genomic fragment or fragments, and wherein the reference genomic fragment or fragments are known to not correspond to the possibly abnormal genomic region; linearizing the plurality of labeled sample molecules or portions thereof in a fluidic channel; linearizing the plurality of labeled reference molecules in a fluidic channel; detecting signals from the labeled sample molecules and labeled reference molecules so as to ascertain at least: a first pattern or plurality of patterns characteristic of the genomic fragment or fragments of interest; and a second pattern or plurality of patterns characteristic of the reference genomic fragment or fragments; and comparing coverage depth for the genomic fragment or fragments of interest to coverage depth for the reference genomic fragment or fragments to determine copy number of the genomic fragment or fragments of interest, wherein the method does not comprise sequencing or assembly. labeling a plurality of sample nucleic acid molecules, each of 500 base pairs or less, with at least a first label, wherein the sample molecules comprise polynucleotide sequences of a genomic fragment or fragments of interest, wherein the sample is derived from maternal blood, and wherein the reference molecules are derived from a maternal sample other than blood, and wherein the genomic fragment or fragments of interest correspond to a possibly abnormal genomic region; providing a plurality of labeled reference nucleic acid molecules, each of 500 base pairs or less, wherein the reference molecules comprise polynucleotide sequences of a reference genomic fragment or fragments, and wherein the reference genomic fragment or fragments are known to not correspond to the possibly abnormal genomic region; linearizing the plurality of labeled sample molecules or portions thereof in a fluidic channel; linearizing the plurality of labeled reference molecules in a fluidic channel; detecting signals from the labeled sample molecules and labeled reference molecules so as to ascertain at least: a first pattern or plurality of patterns characteristic of the genomic fragment or fragments of interest; and a second pattern or plurality of patterns characteristic of the reference genomic fragment or fragments; and a first pattern or plurality of patterns characteristic of the genomic fragment or fragments of interest; and a second pattern or plurality of patterns characteristic of the reference genomic fragment or fragments; and comparing coverage depth for the genomic fragment or fragments of interest to coverage depth for the reference genomic fragment or fragments to determine copy number of the genomic fragment or fragments of interest, wherein the method does not comprise sequencing or assembly.