WHAT GENES SHAPE A FACE?

Mary Marazita

Genomics holds immense potential for intervention and treatment of diseases like cancer and diabetes. Beyond that, genomics also provides insight into how genes influence the structures and appearance of parts of the body—known as morphology. As with other research based in genomics, studying morphology calls for massive data sets and advanced computation.

Mary Marazita studies the genomic markers associated with malformations of the human face and head. Marazita is co-director of the Center for Craniofacial and Dental Genetics (CCDG), as well as Distinguished Professor of Oral Biology in the School of Dental Medicine, and professor of human genetics in the School of Public Health.

“The CCDG primarily studies craniofacial birth defects—such as cleft lip, cleft palate and craniosynostosis, in which the bones of a baby’s skull fuse together before the brain has stopped growing,” Marazita explains. “Complementing that, we study genomic markers associated with normal facial development, and dental and oral diseases such as cavities and periodontal disease. Our mission really is to identify genetic causes of complex human conditions and traits that affect normal development of the craniofacial and oral complexes.”

Having studied the genetic basis of these conditions for more than 40 years in very large population-based studies worldwide, Marazita has seen the capabilities of genomic technology grow exponentially.

“I was trained in human genetics—remember, there was genetics and molecular biology before genomics. It was a largely computational science even though we didn’t have very good computers in those days,” she says.

At that time, the limit of human genetic technology was studying tissues and blood and conducting genetic analyses of the molecules in the samples. Researchers could identify and examine a specific gene found in an animal model and compare it to genes found in human data. Current advanced genomic tools combined with bioinformatics create the possibility of linking genetic information to craniofacial traits, oral disorders and 3D mapping of faces.

Seth Weinberg is co-director of the CCDG, as well as professor in the Departments of Oral Biology, Human Genetics and Anthropology. He led a multiyear, NIH-funded study with John Shaffer, assistant professor of human genetics, which scanned roughly seven million genetic markers in the DNA of more than 8,000 healthy people. The study focused on statistical relationships between shape measurements based on 3D facial images and genetic markers that are known to play roles in creating human physical variation.

“This was the opportunity to build a big data resource,” Weinberg explains. “This resource enabled us to replace old ways of measurement with a repository of three-dimensional facial images with exquisite, detailed measurements linked with DNA samples.” The study was conducted across multiple sites in the United States and United Kingdom, and much of the data lives in usable repositories, from where it is frequently downloaded and used in clinical and other research.

A basic concept underlying this research is that the genes driving human facial shape are the same as those involved in malformations like cleft palate. Therefore, studies of typical facial features can reveal important insights into the biology of related health conditions. Among the surprising insights of the project: the facial feature most influenced by your genes is your nose.

“It’s hard to imagine that data like this has not been around for a long time,” says Weinberg. “The first genetic mapping study of human facial morphology was only in 2012. We have seen a lot of firsts coming in a short time.”