Next of Kin
Although Harley wasn’t yet born, Avery’s discovery would prove to be a seminal moment in his career. As head of OMRF’s Arthritis and Immunology Research Program, his work focuses on pinpointing the genetic roots of lupus, the devastating autoimmune disease that affects as many as 2 million Americans and 15 million people worldwide.
The roots of lupus, like most diseases, are not fully known. But thanks to the work of Harley and others in the field, it is now all but settled that the disease is “multigenic,” meaning that it is caused by defects at multiple sites on the DNA.
Harley spearheaded a massive research effort that involved 150 scientists and staff at more than a dozen institutions in the U.S. and Europe. Using SNP genotyping—the same process that would soon tell me whether I can taste certain bitter flavors or am more likely than average to develop colorectal cancer before the age of 89—the researchers studied the DNA of 720 women with lupus and 2,337 women without lupus (the disease strikes women nine times as frequently as men).
Scanning each subject’s complete sequence of DNA—3 billion chemical pairs that together make up a person’s “genome”—they homed in on 317,000 specific locations where a single unit of DNA might vary from one person to the next. The scientists confirmed these results in another independent set of 1,846 women with lupus and 1,896 women without lupus.
To most, those results would read like alphabet soup, a seemingly senseless concoction of A’s, C’s, G’s and T’s. But to Harley and his research army, the four letters (which stand for adenine, cytosine, guanine and thymine) read like a recipe. And the order in which those ingredients are arranged will determine everything about us, from hair color to susceptibility to disease.
When Harley’s team culled through the seemingly endless data they’d generated, they discovered 13 different regions on the DNA—genes—associated with lupus. These included three genes previously thought unconnected to the disease and a region once believed to be “junk DNA,” a piece of genetic material without a known function. In addition, the scientists uncovered further evidence strengthening the genetic case against nine genes linked to lupus and other autoimmune diseases.
Harley’s work, which appeared in the journal Nature Genetics earlier this year, is one of several recent projects that have made major advances toward unmasking the genetic culprits behind lupus. And later this summer, OMRF’s Dr. Patrick Gaffney will unveil—again in Nature Genetics—a new, genome-wide study that will reveal yet another potential genetic culprit behind lupus.
“We’re making extra-ordinary progress,” says Harley. “Less than a year ago, we were only aware of nine genes that contributed to lupus. Since that, we’ve identified another 16 genes associated with the disease.” These new genetic findings, he says, “have opened many new doors. And we’re excited to investigate what’s behind each of them.”
When my test results arrived in the form of a link from 23andMe, I took a deep breath and clicked. What I expected was a moment of revelation. What I got was decidedly unenlightening: raw data and research studies (like Harley’s) linking this or that genetic sequence to an increased or decreased risk of various medical conditions. I spent the remainder of the day with my head buried in their—my—data, trying to make heads or tails of my genes.
“I’m going to get Lou Gehrig’s disease,” I announced to my wife when I got home from work that evening. “What?! Is that what your report said?” She sat frozen on the edge of our bed. Somehow, taking off her socks had become less important now that I had introduced the specter of the incurable neurodegenerative disease.
“Well, it’s not a lock,” I admitted. “But I am 1.3 times more likely to get it than other people of European descent.” We spent the rest of the night and much of the next few days talking about the test. Some of the information was useless but nonetheless amusing: Apparently, I have wet ear wax and the same fast-twitch muscle SNPs as some Olympic athletes. But most of what I learned was vaguely scary. I say vaguely because I was having trouble understanding what, exactly, it all meant. I say scary because the report contained much discussion of and statistics relating to the risk of contracting just about any disease under the sun.