U Team Looks for Genetic Clues to Organ Rejection

Why do some patients experience kidney transplant rejection while others are able to live with the new organ? That's the question behind one of the latest genetic studies at the University of Minnesota.

The project is a collaboration of William Oetting, an associate professor in the College of Pharmacy, and SPH professor Wei Pan.

Over the past four years, Oetting's lab has collected genetic samples from kidney transplant patients. That data has been handed over to Pan, who will analyze the genes to see which are related to kidney rejection. Similar studies have analyzed anywhere from 30 to 100 patient samples, while this study includes the DNA of more than 500 patients.

"It's probably the largest study of its kind," says Pan. Another "first" will be how the data is analyzed. Pan will create a new statistical method to single out the genes behind organ rejection. Too many statistical possibilities exist to examine every gene and every possible combination of genes in the DNA samples.

"So the question becomes how do you find the relevant genes?" says Pan. "We'll work to develop smarter search methods."

A study challenge involves epistasis, the interaction of genes in the genetic representation of a problem. The higher the epistasis, the harder it is for a statistical model to solve the problem. Because organ rejection is a complex process, there are many genes that lead to it, and thus, a high level of epistasis.

While the researchers will uncover clues to kidney rejection, their findings could also prove useful in identifying genetic variations that contribute to other complex health problems and diseases.