“Master key” for lupus genes could lead to new therapies

Using software designed at OMRF, researchers have identified a common factor present in many lupus-related genes.

The Human Genome Project, a 13-year endeavor that costs millions of dollars, ended in 2003 when scientists sequenced the human genome. Since then, the process has become faster and less expensive, allowing scientists to create vast databases of genetic information in a fraction of the time.

For researchers studying lupus, that resulted in the discovery of 94 genes related to the autoimmune disease. Lupus is an autoimmune disease in which the immune system becomes overactive and confused, attacking the body’s own tissues. The Lupus Foundation of America estimates 1.5 million Americans have lupus.

OMRF scientists Marta Alarcon, M.D., Ph.D., and Mikhail Dozmorov, Ph.D., wanted to know what, if anything, lupus-related genes have in common.

“Think about the genes like locks, which need keys to open,” said Dozmorov. “We were looking for a master key—something that affects all of these genes.”

Using a program called Genome Runner, they searched the Encyclopedia of DNA Elements, or ENCODE, to see what stood out about those genes. They found seven transcription factors that affected a large number of genes. Their research was published in the journal Epigenetics.

“Each cell has the same DNA, but transcription factors tell specific genes to turn on or off, which allows a nerve cell to behave differently from a muscle cell, even though they have the same set of instructions,” Alarcon said.

Researchers hope the transcription factors will provide new targets for treating lupus and other autoimmune diseases, said Dozmorov.

“Then we had another idea,” he said. “If many of these lupus-related genes had these transcription factors in common, maybe we could search for other genes affected by the transcription factors.”

The genes they found are related to the immune system and could play a part in lupus.

Alarcon said the next step is to look at the transcription factors and related genes in patients to see what their role is in the disease.

The research was funded by grants No. P01AI083194 from the National Institute of Allergy and Infectious Diseases and No. P20GM12345 from the National Institute of General Medical Science, part of the National Institutes of Health.