Adding to the mystery, the DNA interval is among the 98 percent of our genome that doesn't code for proteins. Most efforts to determine the function of the genome have focused on the two percent of our DNA that overlaps protein-coding genes. Scientists are just now beginning to explore the non-coding region, once referred to as "junk DNA."

As part of this effort, the Berkeley Lab scientists set out to determine the function of the DNA interval in chromosome 9p21 that's linked to coronary artery disease. They removed an analogous section of DNA from mice, then tracked what happened.

The expression level of two genes located far away, Cdkn2a and Cdkn2b, plummeted by about 90 percent in the "knock-out" mice compared to normal mice. These genes are important in controlling cell cycles and have been linked to cancer when mutated, but they had never been linked to coronary artery disease.

The scientists also studied heart tissue of the "knock-out" mice and found that the smooth muscle cells from their aortas had increased proliferation, a hallmark of coronary artery disease.

"Our research shows that the DNA interval plays a pivotal role in regulating the expression of two genes that control cell cycles. It also suggests that variants of the interval spur the progression of coronary artery disease by altering the dynamics of vascular cells," says Pennacchio.

With this mechanism identified, scientists can develop therapies that fight coronary artery disease by targeting the two genes and jumpstarting them into action, says Pennacchio. He also believes that the genetic roots of many other diseases will be unearthed as scientists learn how to decipher the function of non-coding DNA.

"Non-coding DNA is a huge area of the genome, waiting to be explored, which could have huge dividends for understanding and treating disease," says Pennacchio.

Source: DOE/Lawrence Berkeley National Laboratory