Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New Stanford method enables sequencing of fetal genomes using only maternal blood sample

05.07.2012
Researchers at the Stanford University School of Medicine have for the first time sequenced the genome of an unborn baby using only a blood sample from the mother.

The findings from the new approach, to be published July 4 in Nature, are related to research that was reported a month ago from the University of Washington. That research used a technique previously developed at Stanford to sequence a fetal genome using a blood sample from the mother, plus DNA samples from both the mother and father.

The whole genome sequencing in the new Stanford study, however, did not require DNA from the father — a significant advantage when a child's true paternity may not be known (a situation estimated to affect as many as one in 10 births in this country) or the father may be unavailable or unwilling to provide a sample. The technique brings fetal genetic testing one step closer to routine clinical use.

"We're interested in identifying conditions that can be treated before birth, or immediately after," said Stephen Quake, PhD, the Lee Otterson Professor in the School of Engineering and professor of bioengineering and of applied physics. "Without such diagnoses, newborns with treatable metabolic or immune system disorders suffer until their symptoms become noticeable and the causes determined." Quake is the senior author of the research. Former graduate student H. Christina Fan, PhD, now a senior scientist at ImmuMetrix, and current graduate student Wei Gu are co-first authors of the article.

As the cost of such technology continues to drop, it will become increasingly common to diagnose genetic diseases within the first trimester of pregnancy, the researchers believe. In fact, they showed that sequencing just the exome, the coding portion of the genome, can provide clinically relevant information.

In the new study, the researchers were able to use the whole-genome and exome sequences they obtained to determine that a fetus had DiGeorge syndrome, which is caused by a short deletion of chromosome 22. Although the exact symptoms and their severity can vary among affected individuals, it is associated with cardiac and neuromuscular problems, as well as cognitive impairment. Newborns with the condition can have significant feeding difficulties, heart defects and convulsions due to excessively low levels of calcium.

"The problem of distinguishing the mother's DNA from the fetus's DNA, especially in the setting where they share the same abnormality, has seriously challenged investigators working in prenatal diagnosis for many years," said Diana Bianchi, MD, executive director of the Mother Infant Research Institute at Tufts Medical Center, who was not involved in the Nature study. "In this paper, Quake's group elegantly shows how sequencing of the exome can show that a fetus has inherited DiGeorge syndrome from its mother." (Bianchi is chair of the clinical advisory board of Verinata Health Inc., a company that provides a fetal genetic test using earlier technology developed by Quake.)

Prenatal diagnosis is not new. For decades, women have undergone amniocentesis or chorionic villus sampling in an attempt to learn whether their fetus carries genetic abnormalities. These tests rely on obtaining cells or tissue from the fetus through a needle inserted in the uterus — a procedure that can itself lead to miscarriage in about one in 200 pregnancies. They also detect only a limited number of genetic conditions.

The new technique hinges on the fact that pregnant women have DNA from both their cells and the cells of their fetus circulating freely in their blood. In fact, the amount of circulating fetal DNA increases steadily during pregnancy, and late in the third trimester can be as high as 30 percent of the total.

In 2008, Quake's lab pioneered the use of the relative levels of fetal DNA in maternal blood to diagnose conditions caused by missing or extra chromosomes, such as Down syndrome. Four companies in the United States now market tests based on the technique to physicians and parents, and demand for the service is increasing steadily. (Quake's specific approach was licensed by Stanford to Redwood City-based Verinata and South San Francisco-based Fluidigm Inc. Neither company was involved in the current study.) These tests, however, do not provide a full-genome profile, and cannot identify more-subtle genetic anomalies that occur within chromosomes and other DNA.

This study takes the blood-sampling test one step farther by recognizing that circulating fetal DNA contains genetic material from both the mother and the father. By comparing the relative levels in the mother's blood of regions of maternal (from both the mother and the fetus) and paternal (from the fetus only) DNA known as haplotypes, the researchers were able to identify fetal DNA from the mix and isolate it for sequencing. The method differs from that of the University of Washington group by inferring the father's genetic contribution, rather than sampling it directly (through saliva).

The Stanford team tried its method in two pregnancies. One of the mothers had DiGeorge syndrome; the other did not. Their whole genome and exome sequencing showed that the child of the woman with DiGeorge syndrome would also have the disorder. The finding was confirmed by comparing the predicted fetal genome sequence with the sequence obtained immediately after birth from umbilical cord blood. Although the experiments were performed retrospectively and these women and their babies remained anonymous, a similar finding in a real clinical setting would likely prompt doctors to assess the baby's heart health and calcium levels shortly after birth.

"Three years ago we were very excited about successfully validating non-invasive fetal aneuploidy detection," said study co-author Yair Blumenfeld, MD, a clinical assistant professor of obstetrics and gynecology at Stanford medical school. "But we always knew that detecting fetal chromosomal abnormalities was just the tip of the iceberg, and that diagnosing individual gene defects was the future. This important study confirms our ability to detect individual fetal gene defects simply by testing mom's blood."

The researchers plan to continue to develop the technology for eventual use in the clinic.

In addition to Quake, Gu, Fan and Blumenfeld, other Stanford scientists involved in the research include graduate student Jianbin Wang and professor of obstetrics and gynecology Yasser El-Sayed, MD.

The research was funded with support from the Howard Hughes Medical Institute and the National Institute of Health.

Quake and Fan hold shares in Verinata Health and Fluidigm. Quake is also co-chair of Stanford's Department of Bioengineering, which is run jointly by the schools of Engineering and of Medicine.

The Stanford University School of Medicine consistently ranks among the nation's top medical schools, integrating research, medical education, patient care and community service. For more news about the school, please visit http://mednews.stanford.edu. The medical school is part of Stanford Medicine, which includes Stanford Hospital & Clinics and Lucile Packard Children's Hospital. For information about all three, please visit http://stanfordmedicine.org/about/news.html.

The Stanford School of Engineering has been at forefront of innovation for nearly a century, creating pivotal technologies and businesses that have transformed the worlds of technology, medicine, energy and communications and laid the foundation for Silicon Valley. The school advances modern science and engineering through teaching and research. The school is home to nine departments, 245 faculty and more than 4,000 students, tackling the world's most pressing problems in areas like human health and environmental sustainability. For more information, visit http://engineering.stanford.edu.

Krista Conger | EurekAlert!
Further information:
http://www.stanford.edu
http://engineering.stanford.edu

More articles from Life Sciences:

nachricht Zebrafish's near 360 degree UV-vision knocks stripes off Google Street View
22.06.2018 | University of Sussex

nachricht New cellular pathway helps explain how inflammation leads to artery disease
22.06.2018 | Cedars-Sinai Medical Center

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Temperature-controlled fiber-optic light source with liquid core

In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.

Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...

Im Focus: Overdosing on Calcium

Nano crystals impact stem cell fate during bone formation

Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...

Im Focus: AchemAsia 2019 will take place in Shanghai

Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.

Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...

Im Focus: First real-time test of Li-Fi utilization for the industrial Internet of Things

The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.

Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.

Im Focus: Sharp images with flexible fibers

An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.

Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Munich conference on asteroid detection, tracking and defense

13.06.2018 | Event News

2nd International Baltic Earth Conference in Denmark: “The Baltic Sea region in Transition”

08.06.2018 | Event News

ISEKI_Food 2018: Conference with Holistic View of Food Production

05.06.2018 | Event News

 
Latest News

Graphene assembled film shows higher thermal conductivity than graphite film

22.06.2018 | Materials Sciences

Fast rising bedrock below West Antarctica reveals an extremely fluid Earth mantle

22.06.2018 | Earth Sciences

Zebrafish's near 360 degree UV-vision knocks stripes off Google Street View

22.06.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>