Dec. 8, 2010 -- Using a blood sample from a mother-to-be, Hong Kong researchers have mapped the entire genome of her fetus, potentially opening the door for widespread noninvasive prenatal screening for genetic problems.
''This is indeed the first proof of concept study that genome-wide sequencing of a fetus can be done simply using the mother's blood," says researcher Dennis Lo, MD, the Li Ka Shing Professor of Medicine and professor of chemical pathology of The Chinese University of Hong Kong. The genome refers to all the DNA a person possesses.
The report is published today in Science Translational Medicine.
An expert not involved in the study calls the work pioneering, but like Lo, cautions that more work needs to be done and the technique must be replicated to confirm that it works.
If it bears out, the new technique will provide a noninvasive alternative to current invasive prenatal tests for genetic diseases, such as amniocentesis and chorionic villus sampling (CVS).
Sequencing the Fetal Genome: A Closer Look
Lo and his colleagues evaluated a couple who underwent CVS, wanting to know if their child would have a blood disorder known as B-thalassemia. Those with the condition have defective production of hemoglobin, the protein in red blood cells that carries oxygen to the cells of the body, and get anemia.
In 1997, Lo and his colleagues discovered the presence of ''floating" fetal DNA in the blood of pregnant women. In the years since, researchers have evaluated this DNA to detect many genetic and chromosomal problems in the fetus. But until now, researchers have focused on a single disease or genetic characteristic.
In the new research, Lo took a blood sample from the pregnant woman and sequenced nearly 4 billion DNA molecules, looking for fetal genetic signatures deep within the DNA. The researchers compared the genetic maps of the father and mother, looking for places where the maternal and paternal genetic inheritance differed in the fetus.
"The deciphering of the part that the fetus had inherited from its mother was technically more challenging," Lo says. "This was because the fetal DNA was surrounded by an ocean of DNA that the mother had released from her own cells."
Once they had the genome-wide map of the fetus, they scanned it for genetic variations and mutations.
They found the unborn baby had inherited the B-thalassemia mutation from the father but a normal gene from the mother, making the unborn baby a carrier of the disease.
Noninvasive Prenatal Screening: Perspective
''Noninvasive prenatal diagnosis would allow couples at risk of passing on an inherited condition to their child to avoid a 1% risk of miscarriage associated with invasive diagnostic tests such as amniocentesis," says Caroline Wright, PhD, head of science for the PHG Foundation (Foundation for Genomics and Population Health) in Cambridge, England.
''This pioneering study is the first to produce a genome-wide profile for the fetus from a maternal blood sample, and describes a methodology that is potentially applicable to noninvasive diagnosis of almost any genetic condition, rather than being limited to specific traits (such as the sex of the fetus) like most previous methods."
But she says much larger study is needed to prove the technique's accuracy. Many economic and ethical issues must also be addressed, she says.
Noninvasive Prenatal Testing: Researcher's Caveats
Lo tells WebMD the method is very expensive. "It would probably cost some $200,000 if one were to do what we have done in the paper," he says.
But he expects the cost to come down rapidly in the future. "In a few years' time, sequencing would probably be so cheap that this would no longer be a problem."
Another way to contain costs, he says, is to use ''targeted sequencing," looking at a selected number of genomic regions with disease-causing genes. "If one goes down this pathway, then I would predict that the cost can be reduced by 100 times or so," he says.
The study was funded in part by a research agreement with Sequenom, a San Diego company involved in developing diagnostics for prenatal disorders. Lo reports filing patent applications or holding patents on the analysis of fetal nucleic acids in maternal plasma. He serves as a consultant to Sequenom, is on its clinical advisory board, and holds equities.