Method for determining copy number variations

A method for determining the presence or absence of any one or more different complete fetal chromosomal aneuploidies in a maternal test sample comprising fetal and maternal nucleic acids, said method comprising:

• (a) obtaining sequence information for said fetal and maternal nucleic acids in said sample;
• (b) using said sequence information to identify a number of sequence tags for each of any one or more chromosomes of interest selected from chromosomes 1-22, X and Y and to identify a number of sequence tags for a normalizing segment sequence for each of said any one or more chromosomes of interest;
• (c) using said number of sequence tags identified for each of said any one or more chromosomes of interest and said number of sequence tags identified for said normalizing segment sequence to calculate a single chromosome dose for each of said any one or more chromosomes of interest;
• and
• (d) comparing each of said single chromosome doses for each of said any one or more chromosomes of interest to a threshold value for each of said one or more chromosomes of interest, and thereby determining the presence or absence of one or more different complete fetal chromosomal aneuploidies in said sample.

A method for determining the presence or absence of different partial fetal chromosomal aneuploidies in a maternal test sample comprising a fetal and maternal nucleic acids, said method comprising:

• (a) obtaining sequence information for said fetal and maternal nucleic acids in said sample;
• (b) using said sequence information to identify a number of sequence tags for each of any one or more segments of any one or more chromosomes of interest selected from chromosomes 1-22, X, and Y and to identify a number of sequence tags for a normalizing segment sequence for each of said any one or more segments of any one or more chromosomes of interest;
• (c) using said number of sequence tags identified for each of said any one or more segments of any one or more chromosomes of interest and said number of sequence tags identified for said normalizing segment sequence to calculate a single chromosome dose for each of said any one or more segments of any one or more chromosomes of interest;
• and
• (d) comparing each of said single segment doses for each of said any one or more segments of any one or more chromosomes of interest to a threshold value for each of said any one or more chromosomal segments of any one or more chromosome of interest, and thereby determining the presence or absence of one or more different partial fetal chromosomal aneuploidies in said sample.

A method for determining the presence or absence of any twenty or more different complete fetal chromosomal aneuploidies in a maternal plasma test sample comprising a mixture of fetal and maternal cell-free DNA molecules, said method comprising:

• (a) sequencing at least a portion of said cell-free DNA molecules to obtain sequence information for said fetal and maternal cell-free DNA molecules in said sample;
• (b) using said sequence information to identify a number of sequence tags for each of any twenty or more chromosomes of interest selected from chromosomes 1-22, X, and Y and to identify a number of sequence tags for a normalizing chromosome for each of said twenty or more chromosomes of interest;
• (c) using said number of sequence tags identified for each of said twenty or more chromosomes of interest and said number of sequence tags identified for each said normalizing chromosome to calculate a single chromosome dose for each of said twenty or more chromosomes of interest;
• and
• (d) comparing each of said single chromosome doses for each of said twenty or more chromosomes of interest to a threshold value for each of said twenty or more chromosomes of interest, and thereby determining the presence or absence of any twenty or more different complete fetal chromosomal aneuploidies in said sample.