Study Finds Rare Resistance to Serious Genetic Diseases

Scientists have found a rare genetic resilience that allows people to carry serious disease-causing genes without becoming affected. The results are reported online in the journal Nature Biotechnology. 

There are many, many kinds of genetic conditions. For this study, the scientists focused on a class known as Mendelian disorders (after famed botanist and geneticist Gregor Mendel), which are generally caused by mutations in a single gene. These mutations are considered penetrant: that is, if someone has one of these mutations, they will inevitably develop the associated disease. The researchers looked at eight severe conditions that exclusively affect children: cystic fibrosis, Smith-Lemli-Opitz syndrome, familial dysautonomia, epidermolysis bullosa simplex, Pfeiffer syndrome, autoimmune polyendocrinopathy syndrome, acampomelic campomelic dysplasia, and atelosteogenesis. By focusing on childhood-onset illnesses, the researchers could be sure that their adult study subjects were past the point of developing—or not developing—symptoms.

The study is part of the Resilience Project, which investigates what makes people healthy (as opposed to most medical research, which looks at how and why people get sick). Researchers reviewed the genomic data of 589,306 healthy volunteers from 12 different studies and organizations, including the DNA-testing company 23andMe. Within each genome, the scientists screened 874 genes, looking for mutations associated with disease.

Out of nearly 600,000 healthy participants, just 13 people carried the mutations—but none of them were, or ever had been, sick with any Mendelian condition. Something in their genes had intervened, although we don’t know exactly what that something is yet. The researchers say the findings indicate that perhaps these mutations aren't as penetrant as we thought.

"The identification of resilient individuals may provide a first step toward uncovering protective genetic variants that could help elucidate the mechanisms of Mendelian diseases and new therapeutic strategies," they write.

Unfortunately, those outcomes aren't going to directly result from this study for a very specific reason: the researchers don't know who these 13 resilient individuals are. Attempts to contact them were unsuccessful, in part because the consent forms they signed did not include permission to follow up. The researchers were therefore unable to get more information from these people, or to tell them about their resilience and the mutations they carried.

“There’s an important lesson here for genome scientists around the world: the value of any project becomes exponentially greater when informed consent policies allow other scientists to reach out to the original study participants,” study co-author Stephen Friend said in a press statement. “If we could contact these 13 people, we might be even closer to finding natural protections against disease. We anticipate launching a prospective study in the future that will include a more broadly useful consent policy.”

Still, the study's preliminary results suggest that there are two ways to study a mutation-related condition: through people who have symptoms, and through those who seem healthy.

“Most genomic studies focus on finding the cause of a disease, but we see tremendous opportunity in figuring out what keeps people healthy,” co-author Eric Schadt said. “Millions of years of evolution have produced far more protective mechanisms than we currently understand. Characterizing the intricacies of our genomes will ultimately reveal elements that could promote health in ways we haven’t even imagined.”