October 21, 2011 — A DNA chip created by a Children’s Hospital scientist has been used as an important research tool for geneticists analyzing genes that play a role in heart disease — as well as other complex, common metabolic diseases. Brendan Keating, PhD, of the Center for Applied Genomics at Children’s Hospital, conceived and developed the cardiovascular gene array to collect signals from gene variants that raise the risk of coronary artery disease (CAD) and heart attacks — myocardial infarctions (MI).
How the DNA chip works
The DNA chip, also called an array, contains millions of micron-sized beads holding specific DNA probes for genetic variants of interest. When a test sample (DNA to be analyzed) is brought into contact with the chip, the sites at which test DNA hybridizes (binds) to matching probes in the DNA chip lets researchers identify specific DNA sequences occurring in the test sample.
International scientists use DNA chip in recent studies
An international consortium of scientists, led by British Heart Foundation researchers recently used Keating’s chip to help discover five new gene variants associated with susceptibility to coronary heart disease. When added to existing heart-related genes, the findings may contribute eventually to helping identify individuals at high risk of developing CAD — the most common cause of premature death and disability worldwide. The international consortium announced their findings on Sept. 22 in the open-access journal PLoS Genetics. The new study identified five new gene variants, while showing that the majority of signals from previous smaller, underpowered studies were incorrect.
Keating, a co-author of the study, said, “At the time of the array design in 2006 we had very few robust signals known for CAD and MI, and there was much controversy about the strength of some of the findings already published. This low-cost array allowed many research groups to pool appropriately collected CAD and MI cases and controls, and to meta-analyze these datasets together. This study reinforces the value of large-scale collaboration of international groups in the cardiovascular community to discover new genes that may become useful targets for therapy.”
Keating’s cardiovascular gene chip has also been used for other studies nearing completion by large consortiums, including those investigating type 2 diabetes, stroke, lipids and body mass index.
“We have processed and analyzed many of the DNA samples used in these studies,” said Hakon Hakonarson, MD, PhD, director of the Center for Applied Genomics at The Children’s Hospital of Philadelphia. “We will keep uncovering new disease genes as the sample sizes grow, adding important new information about the gene networks and molecular pathways that underlie many traits of these cardiovascular diseases. This chip is empowering studies that may suggest important targets for future therapeutic interventions.”
John Ascenzi, Children's Hospital of Philadelphia, 267-426-6055, email@example.com