NON-INVASIVE FETAL GENETIC SCREENING BY DIGTAL ANALYSIS

摘要

The present methods are exemplified by a process in which maternal blood containing fetal DNA is diluted to a nominal value of approximately 0.5 genome equivalent of DNA per reaction sample. Digital analysis is then be used to detect aneuploidy, such as the trisomy that causes Down Syndrome. Since aneuploidies do not present a mutational change in sequence, and are merely a change in the number of chromosomes, it has not been possible to detect them in a fetus without resorting to invasive techniques such as amniocentesis or chorionic villi sampling. Digital amplification allows the detection of aneuploidy using massively parallel amplification and detection methods, examining, e.g., 10,000 genome equivalents.

主权项

1. A method for identifying a risk for an aneuploidy on a first chromosome of a fetus carried by mother, the method comprising:
a) providing a sample of nucleic acids derived from a cell-free portion of a maternal blood sample, wherein said sample contains a mixture of maternal and fetal DNA; b) selectively detecting preselected sequences on at least the first chromosome and preselected sequences on a second chromosome in the sample; c) determining a first value for an amount of a first preselected sequence representing a first location on the first chromosome, wherein the first value:
i) includes a contribution from detection of the maternal DNA and the fetal DNA, andii) is not based on separately determining contributions to the amount at the first location from the maternal DNA and the fetal DNA; d) determining a second value for an amount of a second preselected sequence representing a second location on the second chromosome, wherein the second value:
i) includes a contribution from detection of the maternal DNA and the fetal DNA; andii) is not based on separately determining contributions to the amount at the second location from the maternal DNA and the fetal DNA; and e) conducting a statistical analysis to analyze for aneuploidy of the first chromosome in the fetus using the first value, the second value, and one or more additional values for additional samples of nucleic acids derived from cell-free portions of additional maternal blood samples that contain mixtures of maternal and fetal DNA.