As a boy, Patrick Gaffney wandered the meadows of southern Minnesota with his father, each on a quest to find the perfect symbol of their Irish heritage.
“I had no idea then that the four-leaf clover results from a genetic mutation,” said Gaffney, who now researches genetic diseases at the Oklahoma Medical Research Foundation. “I just knew it represented good luck, and I loved the challenge of trying to find one before my dad.”
A physician-scientist, Gaffney leads OMRF’s Genes and Human Disease Research Program, where eight labs, including his own, seek to better understand genetic mutations in humans with less fortunate results than a four-leaf clover.
The three-leaf clover, or shamrock, is a traditional symbol of St. Patrick’s Day. It is a perennial wildflower native to Ireland and other parts of Europe that now grows almost worldwide.
Around one in every 5,000 has four leaves. As with the clover, genetic mutations in humans result from DNA typos.
“Your DNA is sort of like a massive and extremely detailed cookbook for your body, with individual recipes telling your body how to grow, function and repair itself,” said Gaffney, who holds the J.G. Puterbaugh Chair in Medical Research at OMRF.
Everyone has genetic typos, and usually they are benign, meaning they have no harmful effects.
“But imagine if a typo in that cookbook said to add two cups of salt instead of two teaspoons of salt to your favorite potato soup recipe,” Gaffney said. “A typo in our DNA can have consequences far more profound than a pot of inedible soup.”
Gaffney’s lab studies mutations with serious ramifications. For the past 20 years, he has worked to narrow the list of thousands of potential genetic variants linked to the autoimmune disease lupus.
Lupus is a chronic illness that can cause widespread inflammation and organ damage. It affects more than 200,000 Americans, about 90% of whom are female. Existing treatments mainly focus on managing symptoms and preventing flares of the disease.
Gaffney’s task is gargantuan, as the human body has roughly 60 million genetic variants spread across 20,000 different genes. Still, his lab has made significant headway. Computer modeling and advanced gene sequencing technology have helped Gaffney shrink the number of possible variants that trigger the biological processes that lead to lupus.
“Discovering the exact mutations would be the first step in designing more targeted lupus treatments,” he said. “Pinpointing them would be very much like finding a four-leaf clover.”
