Methods for Non-Invasive Prenatal Ploidy Calling

A method for determining presence or absence of fetal aneuploidy in a maternal tissue sample comprising fetal and maternal genomic DNA, the method comprising:

• a) obtaining a mixture of fetal and maternal genomic DNA from said maternal tissue sample;
• b) conducting massively parallel DNA sequencing of DNA fragments randomly selected from the mixture of fetal and maternal genomic DNA of step a) to determine the sequence of said DNA fragments;
• c) identifying chromosomes to which the sequences obtained in step b) belong;
• d) using the data of step c) to determine an amount of at least one first chromosome in said mixture of maternal and fetal genomic DNA, wherein said at least one first chromosome is presumed to be euploid in the fetus;
• e) using the data of step c) to determine an amount of a second chromosome in said mixture of maternal and fetal genomic DNA, wherein said second chromosome is suspected to be aneuploid in the fetus;
• f) calculating the fraction of fetal DNA in the mixture of fetal and maternal DNA;
• g) calculating an expected distribution of the amount of the second target chromosome if the second target chromosome is euploid, using the number in step d);
• h) calculating an expected distribution of the amount of the second target chromosome if the second target chromosome is aneuploid, using the first number is step d) and the calculated fraction of fetal DNA in the mixture of fetal and maternal DNA in step f);
• and
• i) using a maximum likelihood or maximum a posteriori approach to determine whether the amount of the second chromosome as determined in step e) is more likely to be part of the distribution calculated in step g) or the distribution calculated in step h);
• thereby indicating the presence or absence of a fetal aneuploidy.