Non-Invasive Fetal Genetic Screening by Digital Analysis

Abstract

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 PCR 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.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims priority from U.S. Provisional Patent Application No. 60 / 764,420 filed on Feb. 2, 2006, and U.S. Utility patent application Ser. No. 11 / 701,686, filed Feb. 2, 2007, which are hereby incorporated by reference in their entirety.STATEMENT OF GOVERNMENTAL SUPPORT[0002]This invention was made with U.S. Government support under contract 0535870 awarded by the National Science Foundation. The U.S. Government has certain rights in this invention.REFERENCE TO SEQUENCE LISTING[0003]Applicants assert that the paper copy of the Sequence Listing is identical to the Sequence Listing in computer readable form found on the accompanying computer file. Applicants incorporate the contents of the sequence listing by reference in its entirety.BACKGROUND OF THE INVENTION[0004]1. Field of the Invention[0005]The present invention relates to the field of fetal genetic screening and to the field of quantitative nucleic acid analysis.[0006]2...

AI Technical Summary

Benefits of technology

"The present invention is a method for detecting target sequences in a mixture of maternal and fetal genetic material. The method involves obtaining genetic material from maternal peripheral blood or blood plasma, which contains both maternal and fetal genetic material. The genetic material is then distributed into discrete samples, where each sample contains, on average, one target sequence per sample. The target sequences are detected using a sequence-specific reactant directed to each target sequence. The results are analyzed to determine the presence or absence of the target sequences and the number of results from the discrete samples. The method can be performed with fluorescent techniques and can detect abnormal fetal genetic material. The number of discrete samples used in the method depends on the desired statistical significance and can range from about 500 to 10,000 or more. The method can be used for prenatal diagnosis and screening purposes."

Problems solved by technology

The PCR method may be (but is not necessarily) quantitative.

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