Diagnosing fetal chromosomal aneuploidy using massively parallel genomic sequencing

A method for performing prenatal diagnosis of a fetal chromosomal aneuploidy in a fetus by analyzing a biological sample obtained from a female subject pregnant with the fetus, wherein the biological sample includes nucleic acid molecules from the female subject and from the fetus, the method comprising:

• sequencing a plurality of the nucleic acid molecules contained in the biological sample to obtain paired sequence reads and paired sequenced tags for each of the plurality of nucleic acid molecule;
• aligning the paired sequenced tags to chromosomes from which the nucleic acid molecules originate;
• determining a count for each of the aligned paired sequenced tags;
• determining a first amount of aligned paired sequenced tags identified as originating from a first chromosome;
• determining a second amount of aligned paired sequenced tags identified as originating from one or more second chromosomes, wherein the determination of the first amount and the second amount is based on the determined counts of the corresponding paired sequenced tags;
• determining a parameter from the first amount and the second amount;
• comparing the parameter to one or more cutoff values;
• and
• based on the comparison, determining a classification of whether a fetal chromosomal aneuploidy exists for the first chromosome.