A Houston molecular biologist dreams of the day he can translate his laboratory research into solid programs to prevent birth defects. But until then, Richard Finnell of The Texas A&M University System Health Science Center’s Institute of Biosciences and Technology (IBT) is using special mice and human DNA samples to pursue the relationship between vitamin deficiency and environmental toxins and common congenital malformations of the heart, spine and palate.
A report of Finnell’s work will be published in this month in the journal, Birth Defects Research (dated March 2003).
Congenital heart defects are the most common of all human birth defects and are the leading cause of death from birth defects during the first year of life, according to the American Heart Association. Out of 1,000 births, eight babies will have some form of congenital heart disorder. About 35,000 babies are born in the U.S. with a defect each year. In addition to these types of birth defects, Finnell’s IBT lab also focuses on neural tube defects, such as spina bifida, and craniofacial defects like cleft palate, conditions which cripple and disfigure thousands of babies each year.
Finnell, director of IBT, is in his second year as leading investigator of a $5.6 million, five-year federal program project grant awarded by the National Heart, Lung and Blood Institute of the National Institutes of Health to IBT, the University of Nebraska Medical Center and the California Birth Defects Monitoring Project.
“Our three research teams will investigate the various ways that selected genes interact with specific drugs, environmental exposures and vitamin deficiencies to cause abnormal heart development,” says Finnell. “Right now we are simply unable to predict when birth defects will occur, based upon either genetic makeup or environmental exposures. But at the end of our five-year project, we hope to be in a position to bring a whole new light on the causes of these significant heart defects, and this, in turn, will significantly increase our ability to prevent them. I would not at all be surprised to find that many of these birth defects have a basic common cause.”
One common cause being pursued by Finnell is the mechanism by which folate (part of the B vitamin complex) is transported through the cells in the developing embryo. Folate provides simple carbon atoms for the body, used as building blocks for important molecular structures. According to Finnell, folic acid was recognized over 10 years ago as a risk modulator for spinal defects, and his experiments with mice genetically altered to remove genes regulating cells’ ability to capture folate have produced embryos with neural, craniofacial and cardio defects. His research is also bolstered by analysis of DNA data from studies of women who are from populations with high rates of neural tube defects and who have been given folate supplements. The studies, from California, Texas and China, indicated that women who took the supplements reduced their risks of giving birth to babies with heart, neural tube or craniofacial defects by as much as 70 percent.
“Part of the problem in isolating causes, however, is that neural tube defects, for example, can occur despite folate sufficiency,” Finnell observed. “Spina bifida, one of the common neural tube defects, has complicated genetics. It’s not like the one gene that determines Huntingdon’s chorea or a chromosomal abnormality like Down syndrome. Several genes appear to interact with environmental factors, thus the problem must involve how folate is transported in the cells, and two or three different genes must be involved.”
One possible explanation is that the genes in question code for a protein receptor on the cell membrane that catches folate. Changes in the genetics make the receptor less functional at capturing folate, leading to birth defects.
“We need to understand how the protein receptor is made by the gene,” Finnell observed. “Maybe the gene itself is fine, but the protein-making mechanism is somehow defective. The folate-binding receptor gene also does more than just regulate folate uptake; it also functions to determine when other genes are ‘turned on’ through a form of cellular signaling to regulate the formation of anatomical features of the developing embryo.
“Folic acid has been part of multivitamins for decades, and here in the U.S. we’ve been supplementing all grains and cereals with it since 1998,” Finnell said. “But not everyone will take their vitamins or eat a diet with sufficient folate, so we’re also investigating substitutes available from common foods. For example, the compound methionine serves the same biochemical function as folate and is abundant in eggs, so maybe encouraging pregnant women to eat more eggs could provide another solution to reducing birth defects.”
The Texas A&M University System Health Science Center provides the state with health education, outreach and research. Its five components located in communities throughout Texas are Baylor College of Dentistry, the College of Medicine, the Graduate School of Biomedical Sciences, the Institute of Biosciences and Technology and the School of Rural Public Health.

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