Genetic Roots of Cleft Lip and Palate Investigated

Courtesy of the Centers for Disease Control and Prevention, National Center on Birth Defects and Developmental Disabilities.


Courtesy of the Centers for Disease Control and Prevention, National Center on Birth Defects and Developmental Disabilities.

Cleft lip and palate are among the most common birth defects, affecting about one in 700 babies. While smoking during pregnancy and other factors can contribute to its development, genetics are believed to be behind them at least in part in about 70% to 80% of cases. Researchers led by the University of Pittsburgh will explore these genetic causes of cleft lip and palate as well as treatments.

“In addition to looking at variations in genes that might lead us to treatments, we’re also looking for answers for parents who have a child with a cleft and want to know if any future children are at risk,” said principal investigator Eleanor Feingold, PhD, professor of human genetics and senior associate dean at the university’s graduate school of public health.

“This project will help us improve genetic counseling so we can tell parents if their family is predisposed to cleft lips and palates or if it’s a genetic aberration that is highly unlikely to happen again,” said Feingold.

The research will sequence the whole genomes of 430 children with clefts, as well as the genomes of their parents. According to the National Institutes of Health, which is funding the project under the Gabriella Miller Kids First Research Act, it is among the largest whole genome sequencing efforts to examine an oral condition that it has ever initiated.

“The sequencing will provide a wealth of data that will be made available to scientists everywhere, providing the basis for years of research into causes, prevention, and treatment of cleft lip and palate,” said project director and principal investigator Mary L. Marazita, PhD, professor and vice chair of the university’s school of dental medicine department of oral biology and director of its center for craniofacial and dental genetics.

Marazita has studied cleft lip and palate since the 1980s and has developed a database of almost 6,000 families with the condition. The researchers will search the database for “trios,” or mothers, fathers, and children all with cleft lip or palate. These trios will have their whole genomes sequenced to find the variations causing the child’s cleft. Researchers then will be able to determine if the cleft arose spontaneously or if it was from a variant passed along by a parent.

The DNA samples for 430 trios will be sent to the McDonnell Genome Institute at Washington University in St. Louis for sequencing. In about 3 months, the researchers will get the information and share it through a centralized data repository. Marazita expects to get more than 200 terabytes of data to mine, with assistance from about 2 dozen co-investigators and collaborators at nationwide institutes.

“It takes a village to do this kind of work, and we are eager to tackle it,” said Marazita.

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