Determination of fetal aneuploidies by massively parallel DNA sequencing

US8008018B2 · kind B2 · utility

Assignee

• The Board of Trustees of the Leland Stanford Junior University · US

Inventors

• Stephen R. Quake · Pasadena, US
• Hei-Mun Christina Fan · Fremont, US

Key dates

• Filing date: Feb 26, 2009
• Grant date: Aug 30, 2011
• Expiry date: Feb 26, 2029

Classification

• Technology area (CPC Y): Emerging Cross-Sectional Technologies
• CPC primary: Y10T436/143333
• WIPO field: Biotechnology
• WIPO sector: Chemistry

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.