Genes are tiny molecular structures. But they can require huge teams of scientists to unravel their mysteries.
This week, a group of nearly 50 scientists from 33 institutions in the U.S. and abroad announced they had identified a genetic variant associated with lupus and, potentially, heart disease and certain kinds of cancer. OMRF scientists Patrick Gaffney, M.D., and Kathy Moser, Ph.D., led the research, which appears in the newest issue of the American Journal of Human Genetics.
The scientists analyzed massive amounts of data gathered from blood samples donated by patients with lupus, a disease in which the immune system mistakenly turns its defenses against the body.
“With more than 15,000 donated samples, this is the largest genetic experiment ever done in the field of lupus research,” Gaffney said. “We worked with scientists from Spain, Colombia, Canada, England, Sweden, Puerto Rico and all across the U.S. to make this happen.”
Collaborators around the globe sent samples to be analyzed alongside the thousands already housed at OMRF.
“It took a year just to get everything organized,” said Moser, director of the Lupus Family Registry and Repository based at OMRF. “In addition to getting the samples, we worked with researchers to design the experiment and figure out which genes to look at.”
Humans carry an estimated 30 million genetic variants, areas in which their DNA potentially differs from the rest of the population. Using clues from previous experiments, the researchers narrowed their studies to a small fraction—30,000—of those genetic regions with suspected links to lupus.
Still, that meant running genetic analyses to generate 450 million data points. Using 96 samples at a time, a series of robots processed the DNA to incorporate fluorescent colors depending on what genetic variant was present. A laser was then used to capture the information and generate the genetic data.
Each 96-sample batch took a total of four days to process with the staff working 7 days a week for more than 8 months to finish gathering data. Then scientists utilized analytical software to test the 30,000 genetic variants for a relationship to lupus.
Through this process, Moser and the other scientists eventually pinpointed a region near a gene—known as CD44—where variation was associated with an increased risk of lupus. They also believe that changes in this genetic region may be linked to heart disease and cancers of the breast, colon, brain, prostate and others.
“People have been studying the effects of CD44 in autoimmunity for years, but we’re the first ones to find a genetic basis for it,” said Hal Scofield, M.D., of OMRF, who also played a major role in the research. “This discovery could play a part not just in future lupus research but in understanding heart disease and cancer, as well.”
The understanding of lupus genetics has improved dramatically since 2007, when scientists only knew about 7 lupus genes. Collaborations led by OMRF scientists have helped identify 23 more genes since then.
“With this new discovery, we’ve added another gene to the list,” said Moser. “But we already know from ongoing studies there will be more to come.”
By better understanding the role of specific genes in lupus, researchers open doors to much needed improvement in methods of diagnosis and therapies for treating the disease.
OMRF scientists Chris Lessard, Ph.D., and Ken Kaufman, Ph.D., were also integral to the research. The majority of the funding for the research was provided through grants from the National Institute of Arthritis, Musculoskeletal and Skin Diseases and the National Institute of Allergy and Infectious Diseases.
“A project this big, with so many different people all over the world involved, is extremely challenging,” Moser said. “But all the effort and the time seem so worthwhile when you have results that bring us closer to making our patients’ lives better.”