Navigation Links
New Stanford method enables sequencing of fetal genomes using only maternal blood sample
Date:7/4/2012

STANFORD, Calif. -- 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.


'/>"/>

Contact: Krista Conger
kristac@stanford.edu
650-725-5371
Stanford University Medical Center
Source:Eurekalert

Related medicine news :

1. Stanford Woods Institute for the Environment announces 2012 Environmental Venture Project awards
2. Stanford study shows opiates side effects rooted in patients genetics
3. Proposed testosterone testing of some female olympians challenged by Stanford scientists
4. Stanford researchers discover the African cichlids noisy courtship ritual
5. Antioxidant shows promise as treatment for certain features of autism, Stanford study finds
6. New type of retinal prosthesis could better restore sight to blind, Stanford study says
7. Invasive heart test being dramatically overused, Stanford study shows
8. Electronic data methods research seeks to build a learning health care system
9. New delivery method improves efficacy of 2 common Parkinsons disease medications
10. Quick-Reversal Method May Be at Hand for New Blood Thinner
11. Safer Grilling Methods Might Cut Cancer Risk
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/10/2016)... ... February 10, 2016 , ... A ... Ohio Safety Congress and Expo event March 9-11, 2016. Hosted by Ohio's Bureau ... Center. , As the longest running and largest worker's compensation event in ...
(Date:2/10/2016)... MD (PRWEB) , ... February 10, 2016 , ... ... to make Everseat digital self-scheduling readily available to physicians. The integration ... patients can find and select appointments via Everseat’s free mobile app. , The ...
(Date:2/10/2016)... ... February 10, 2016 , ... ... Jacksonville, FL 32224, February 26th: Amateur & Professional Divisions - Time: 7:00pm ... 7:00pm – 10:00pm | Ticket Prices $30, Social Media: http://www.USPoleSportsFed.org , ...
(Date:2/10/2016)... ... 10, 2016 , ... Workrite Ergonomics, who is celebrating their 25th year of ... to being an internationally recognized leader in their industry. , "We are very proud ... President of Workrite. “Workrite recognized the importance of good ergonomics before most of ...
(Date:2/10/2016)... ... February 10, 2016 , ... Anxiety of older Americans over ... of Medicare Part D a decade ago, according to The Senior Citizens League ... on how they are coping with rapidly rising costs. “The implications are chilling, ...
Breaking Medicine News(10 mins):
(Date:2/9/2016)...  Bluestar Silicones will promote its Silbione® Biomedical ... implant applications and announce certification of its clean ... West Conference (Booth #1759), February 9-10, at the ... --> Available in 01 through 70 ... physical properties enabling our customers to optimize their ...
(Date:2/8/2016)... -- Alzheimer Diagnostic Tests - Medical Devices Pipeline ... sector report , "Alzheimer Diagnostic Tests - Medical ... Alzheimer Diagnostic Tests currently in pipeline stage. ... products with comparative analysis of the products at ... players involved in the pipeline product development. It ...
(Date:2/8/2016)... Devices - Medical Devices Pipeline Assessment, 2015 Summary ... Medical Devices Pipeline Assessment, 2015" provides an overview of ... This report is prepared using data sourced from in-house ... industry experts. *Note: Certain sections in the report ... and relevance of data in relation to the equipment ...
Breaking Medicine Technology: