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Study may lead to non-invasive genetic test for fetuses

University of Iowa researchers collaborated on a study led by University of Washington scientists that one day could lead to a single, non-invasive genetic test during pregnancy to identify thousands of disorders in unborn babies.

Using samples from the Maternal Fetal Tissue Bank in the UI Department of Obstetrics and Gynecology and the UI Institute for Clinical and Translational Science (ICTS) Neonatal Biorepository, scientists have successfully sequenced the genome of a baby in the womb without tapping its protective fluid sac. This non-invasive approach to obtaining the fetal genome is reported in the June 6 issue of Science Translational Medicine, a journal of the American Association for the Advancement of Science.

Maternal blood sampled at about 18 weeks into the pregnancy and a paternal saliva specimen contained enough information for the scientists to map the fetus' DNA. This method was later repeated for another expectant couple closer to the start of their pregnancy. The researchers checked the accuracy of their genetic predictions using umbilical cord blood collected at birth, provided by the ICTS Neonatal Repository.

"This study illustrates the critical importance of having repositories with data and samples available to take advantage of evolving technologies as quickly as possible to improve the lives of women and children,” says Jeffrey Murray, M.D., UI professor of pediatrics who leads the ICTS Neonatal Repository. "It has been the willing participation of Iowa families that has enabled this study to be successful and to provide the promise for a brighter future for our families."

The repository, supported in part by a National Institutes of Health sponsored Clinical and Translational Science Award was established in 1999 to provide data and samples from newborn infants and their parents to researchers investigating the causes of and treatments for diseases in newborns.

UI scientists Mark Santillan, M.D., and Donna Santillan, Ph.D., in obstetrics and gynecology, head up the Women's Health Tissue Repository. They worked closely with Murray and the ICTS Neonatal Repository to provide the maternal blood samples for this study. The Women’s Health Tissue Repository includes four tissue banks designed to help researchers study a variety of issues affecting women's health including a maternal fetal tissue bank, a reproductive endocrinology and infertility tissue bank, a well women bank, and an oncology tissue bank. Women receiving obstetric care at UI Hospitals and Clinics can consent for the Maternal Fetal Tissue Bank to collect extra blood, urine, and other specimens, including cord blood, maternal blood, and placenta.

The new study was led by Jacob Kitzman and Matthew Snyder, who work in the laboratory of Jay Shendure, M.D., Ph.D., associate professor of genome sciences at the University of Washington.

Screening Fetal DNA

Scientists have long known that starting a few weeks after conception, a pregnant woman's blood plasma contains cell-free DNA from her developing fetus. Several research groups are currently developing tests to screen this fetal DNA for major abnormalities in the fetus's genetic makeup. Such tests are considered a safer substitute for the more invasive amniocentesis test that samples of fluid from the uterus. These new tests search for just a few genetic disorders or specific congenital abnormalities. For example, a test targeted for Down syndrome would look for evidence of three copies of chromosome 21.

What distinguishes the University of Washington team's latest methods is the ability to assess many and more subtle variations in the fetus' genome, down to a minute, one-letter change in the DNA code.

"This work opens up the possibility that we will be able to scan the whole genome of the fetus for more than 3,000 single-gene disorders through a single, non-invasive test," Shendure says.

 The new technique advances efforts to screen fetal genomes in two ways -- it is able to pick out the parts of the baby's genetic material inherited from each parent with over 98 percent accuracy, and it is able to identify new genetic variations that the fetus does not share with either parent.

Although technical and analytical difficulties still exist, the results suggest that a more refined, less costly version of this approach might make prenatal genetic screening vastly more comprehensive.

However, Shendure also noted that using genome sequencing to predict and communicate risk to patients would be hard in a clinical setting, due to limited knowledge about multi-gene diseases and their many contributing factors beyond genetics.

"The capacity of genomics to generate data is outstripping our ability to interpret it in ways that are useful to physicians and patients," Shendure says, "Although the non-invasive prediction of a fetal genome is now technically feasible, its interpretation --even for single-gene Mendelian disorders -- will remain an enormous challenge."

The project was supported in part by a grant from the National Human Genome Research Institute at the National Institutes of Health and a gift from the Washington Research Foundation.

Story Source: University of Iowa Institute for Clinical and Translational Science

Media Contact: Jennifer Willis,