New prenatal blood test for down syndrome


New prenatal blood test for down syndrome


US scientists have developed a non-invasive way to detect chromosomal disorders such as Down Syndrome in a fetus that only needs a sample of the pregnant woman's blood and therefore does not carry the risk of miscarriage of more invasive methods.

The new method is the work of scientists at Stanford University and Lucile Packard Children's Hospital in California, and the Howard Hughes Medical Institute in Chevy Chase, Maryland, and was published online on 6 October in the Proceedings of the National Academy of Sciences.

Co-author Dr Yair Blumenfeld, a postdoctoral medical fellow in obstetrics and gynecology at Stanford said:

"Right now, people are risking their pregnancies to get this information."

Amniocentesis and chorionic villus sampling, the current prenatal gene testing methods, require the insertion of a needle into the uterus and increase the risk of miscarriage by about half a per cent.

Senior author Dr Stephen Quake, professor of bioengineering at Stanford said non-invasive testing was safer than current methods. He and his team also hope that this method, which looks for fragments of fetal DNA in the pregnant woman's blood, can be done much earlier in the pregnancy.

Human beings usually inherit 23 chromosomes from each parent, making a total of 46. When errors in chromosome numbers occur, they can alter mental and physical development, as in Down Syndrome which results when the fetus inherits three instead of two copies of chromosome 21.

The new method scans for occurrences of fetal aneuploidy, an abnormality in the number of fetal chromosomes in the pregnant woman's blood.

While other scientists have struggled to do this by trying to distinguish between maternal and fetal DNA, Quake, Blumenfeld and colleagues found a way to count errors in chromosome numbers that avoids having to do this.

For the study, they used blood samples from 12 women already known to have aneuploid pregnancies and 6 with normal pregnancies. They then separated the blood into plasma and cells and discarded the cells. This meant they could focus on scraps of DNA floating around in the plasma without being distracted by the DNA of the cells.

The team found that the DNA scraps floating around in the plasma, which came from both the pregnant woman and the fetus, were about 25 to 30 base pairs long, which is long enough to match each scrap to a specific chromosome. By tallying up how many gene scraps came from each chromosome they found that women with Down Syndrome pregnancies had more scraps of chromosome 21 DNA floating in their plasma tha the women with normal pregnancies.

The DNA identification method they used is called "high-throughput shotgun sequencing technology", which basically means they were quickly able to sequence over 5 million sequence tags per patient sample and thereby measure any over- and under-representation of chromosomes from an aneuploid fetus.

The researchers said they were also able to detect other types of aneuploidy (abnormal number of chromosomes), and because fetal DNA starts showing up in maternal blood quite early in the pregnancy, it should be possible to do this test much earlier than the current more invasive methods.

In total, Quake and colleagues "successfully identified all nine cases of trisomy 21 (Down syndrome), two cases of trisomy 18 (Edward syndrome), and one case of trisomy 13 (Patau syndrome)" among the 18 normal and aneuploid pregnancies, some as early as the 14th week of gestation.

Quake said the method should be a great advantage to women, both for those who may wish to terminate and those who may wish to continue with an aneuploid pregnancy.

"The earlier you know you've got a fetus with Down syndrome, the better able you are to prepare," said Quake.

Quake and colleagues now want to repeat the study with a larger number of women. If it passes this test, the new method could be developed into a relatively low cost test for use in clinical settings, but even if the larger scale trial is successful, the new method is unlikely to be available for two or three years yet, said Quake, who added that:

"This technique is on the leading edge of a flood of different ways that rapid DNA sequencing will be used in medicine."

The reserchers reported that the new method also allowed them to "study the characteristics of cell-free plasma DNA", and they found evidence that "this DNA is enriched for sequences from nucleosomes". (Nucleosomes are the tightly packed bundles of chromosomal DNA found in the nuclei of cells).

Stanford is already filing for a patent on the new method, and Quake and other members of the team are consulting for two potential licensees.

"Noninvasive diagnosis of fetal aneuploidy by shotgun sequencing DNA from maternal blood."

H. Christina Fan, Yair J. Blumenfeld, Usha Chitkara, Louanne Hudgins, and Stephen R. Quake.

Proceedings of the National Academy of Sciences, published online October 6, 2008.

doi:10.1073/pnas.0808319105

Source: Stanford University Medical Center, journal abstract.


New Down's syndrome blood test raises hopes and fears. (Video Medical And Professional 2018).

Section Issues On Medicine: Women health