NON-INVASIVE PRENATAL DIAGNOSIS OF SINGLE GENE DISORDERS USING DROPLET DIGITAL PCR

NON-INVASIVE PRENATAL DIAGNOSIS OF SINGLE GENE DISORDERS USING DROPLET DIGITAL PCR

Researchers at the Chan Zuckerberg Biohub and Stanford have developed non-invasive methods for detection of fetal autosomal recessive and X-linked diseases during pregnancy.

Pre-natal diagnosis of single gene disorders often requires the use of invasive techniques such as amniocentesis or chorionic villus sampling (CVS).  These methods have a risk of miscarriage and can only be implemented during certain time windows of pregnancy.  The presence of circulating cell-free DNA of fetal origin in maternal plasma has allowed the development of non-invasive prenatal testing of common aneuploidies (e.g., Down’s syndrome).  The inventors have now shown that circulating cell-free DNA of fetal origin can be used to detect and diagnose inherited single gene disorders, in particular autosomal recessive and X-linked disorders, using droplet digital PCR. 

Stage of Research

The inventors have developed a method to measure the fetal fraction and total amount of cell-free DNA in maternal plasma samples using a multiplexed single-nucleotide polymorphism panel for digital droplet PCR.  The ratio of healthy and diseased alleles in maternal plasma is quantified using TaqMan assays targeting the mutations carried by the parents, in order to provide a diagnosis as early as week 11 of the pregnancy.

Applications

  • Non-invasive, pre-natal detection and diagnosis of autosomal recessive diseases
  • Non-invasive, prenatal detection and diagnosis of x-linked diseases

Advantages

  • Non-invasive
  • Early pregnancy monitoring
  • Maternal blood samples

Stage of Development

Research - in vitro

Publications

Camunas-Soler J, Lee H, Hudgins L, Hintz SR, Blumenfeld YJ, El-Sayed YY, Quake SR. Noninvasive prenatal diagnosis of single-gene disorders by use of droplet digital PCR. Clin Chem 64(2):335-345 (2018)

PCT publication WO2019/010456

Related Web Links

https://quakelab.stanford.edu

Keywords

Droplet digital PCR, circulating cell-free DNA, cell-free DNA, cfDNA, prenatal diagnosis, fetal diagnosis, maternal plasma, maternal blood, autosomal recessive, x-linked

Reference

 Chan Zuckerberg CZB-101S, Stanford S17-227

Patent Information:
For Information, Contact:
CZBiohub Admin
Inteum Hosted Admin
CZ Biohub
ip@czbiohub.org
Inventors:
Stephen Quake
Joan Camunas-Soler
Keywords:
Autosomal Recessive
Cell-Free DNA
cfDNA
Circulating Cell-Free DNA
Droplet Digital PCR
Fetal Diagnosis
Maternal Blood
Maternal Plasma
Prenatal Diagnosis
X-Linked