Unraveling the genetic underpinning of disease

While the protein coding sequence of the human genome is well understood, there is still a great deal to learn about the intergenic regulatory portion of the genome and its role in disease, says Michael Beer, assistant professor of biomedical engineering.

Under a five-year National Institutes of Health grant, Beer will focus on developing computational models that will identify and predict which sequences within the genome are responsible for controlling gene expression. Beer, who works at the McKusick-Nathans Institute of Genetic Medicine, is the principal investigator in the effort.

“We know there are regions within the genome that turn genes on and off,” Beer says. “But we don’t have a full understanding of how or why these sequences have this effect. My grant aims to develop computational and mathematical models to understand how the genome controls protein expression in different cell types.”

Beer’s goal is to bridge the gap between the many standard genetic variations in humans and find those that cause association with susceptibility to diseases. “We know that portions of the genome are shared among individuals who have specific diseases,” he says. “Most common diseases are caused by inappropriate quantities of proteins in cells. The genomic regulatory sequences set the amount of protein in each cell; therefore it’s widely believed that if we understand regulatory sequences we will understand which parts of the genome contribute to specific diseases.”