Patent Document ID: 9657342
Application ID: 12958353
Patent Flag: 1

Claim One:
1. A method for determining a fetal aneuploidy of chromosome 21 in a maternal test sample comprising a mixture of fetal and maternal nucleic acid molecules, said method comprising the steps: (a) preparing a sequencing library from said mixture of fetal and maternal nucleic acid molecules in said maternal test sample, wherein preparing said library comprises the consecutive steps of end-repairing, dA-tailing and adaptor ligating said nucleic acids, wherein said consecutive steps exclude purifying the end-repaired products prior to said dA-tailing and exclude purifying the dA-tailing products prior to said adaptor-ligating; (b) sequencing at least a portion of said nucleic acid molecules from said sequencing library thereby obtaining sequence information for a plurality of fetal and maternal nucleic acid molecules of a maternal test sample; (c) using the sequence information obtained in step (b), identifying a number of sequence tags for at least one normalizing chromosome and for chromosome 21, wherein said at least one normalizing chromosome is a chromosome or a group of chromosomes selected from the group consisting of chromosome 9, chromosome 1, chromosome 2, chromosome 11, chromosome 12, and chromosome 14; (d) using the number of sequence tags identified for chromosome 21 and the number of sequence tags identified for the at least one normalizing chromosome in step (c) to calculate a chromosome dose for chromosome 21, wherein said chromosome dose is a ratio of the number of sequence tags identified for chromosome 21 and the number of sequence tags identified for said at least one normalizing chromosome; and (e) comparing said chromosome dose to at least one threshold value, and thereby identifying the presence or of chromosome 21.