Hundreds of diseases have been linked to genetic factors, but now scientists say they’ve found some people who stay healthy even though they have disease-causing genes.
So what’s their secret?
If researchers could answer that question, they might be able to come up with new treatments and even cures for gene-linked maladies such as cystic fibrosis, Huntington’s disease or sickle-cell anemia.
The good news is that researchers have identified 13 adults who are resilient to severe childhood diseases that are in their genes. In a study published by Nature Biotechnology, researchers report that the 13 were found by analyzing genetic data from nearly 600,000 individuals.
The bad news is that it’s impossible to get back in touch with those lucky 13. When they gave their DNA samples to be analyzed, they didn’t give their consent to be recontacted. As a result, they’ll have to remain anonymous.
“It’s almost as if you got to take the wrapping off the box, and you couldn’t open the box up,” said study co-author Stephen Friend, president of Seattle-based Sage Bionetworks.
There’s still hope, however: Heartened by their initial results, Friend and his colleagues at the Icahn Institute for Genomics at Mount Sinai are setting up a follow-up study known as the Resilience Project, which will have participants submit their genetic data with the understanding that they can be recontacted if something interesting turns up.
The Nature Biotechnology study touches on the challenges as well as the potential payoffs in the search for resilient people.
The research team started out with genomic data from a dozen studies, including more than 400,000 entries from the 23andMe customer database. The 589,306 data sets were screened for the presence of 874 genes that have been linked to 584 Mendelian childhood diseases.
The first round of analysis turned up nearly 16,000 promising candidates. But further filtering and double-checking turned up uncertainties about genetic data, or about clinical diagnoses. As a result, the pool of solid candidates was gradually reduced to the final 13.
Each of the 13 healthy adults carried the genes for one of eight childhood disorders that would typically lead to severe disease before the age of 18: cystic fibrosis, Smith-Lemli-Opitz syndrome, familial dysautonomia, epidermolysis bullosa simplex, Pfeiffer syndrome, autoimmune polyendocrinopathy syndrome, acampomelic campomelic dysplasia and atelosteogenesis.
Friend said there wasn’t enough information about the individuals to determine why they were resilient to those diseases. It could be due to unusual environmental factors, or a rare combination of genetic twists that block the activity of the disease-causing gene. For example, researchers have already identified mutations that provide some protection from sickle-cell anemia and high cholesterol.
“The concept that mutations can be beneficial … gives a reason to look at individuals who are normal and to try to find ways of prevention,” Friend said.
The fact that the people who provided the genetic information for the study couldn’t be recontacted raises a couple of important caveats, Daniel MacArthur of Massachusetts General Hospital said in a Nature Biotechnology commentary. There’s a chance that some resilient individuals may have been missed, or that some of the 13 cases may be “mirages,” he said.
MacArthur said it was sobering to note that only 13 prospects turned up out of a genetic database representing more than a half-million individuals.
“This suggests that even with a million properly consented and deeply sequenced samples, it is extremely unlikely that enough genetic superheroes will be detected to enable a statistically well-powered genome-wide search for the genetic variants that modify disease genes,” he said.
Nevertheless, Friend was hopeful that the Resilience Project would blaze a trail for future big-data projects, as well as medical studies designed to translate genetic findings into therapies. He said that could involve taking DNA samples from resilient individuals, using that DNA to reprogram stem cells in the lab, and then using gene-editing tools to zero in on molecular twists that may ward off disease.
It may sound as if researchers will be looking for a needle in the haystack of the human genome. But Friend told GeekWire that he was confident that the search could identify “which of these small needles may be the ones that are most important.”
Friend is among 30 co-authors of the Nature Biotechnology paper, titled “Analysis of 589,306 Genomes Identifies Individuals Resilient to Severe Mendelian Childhood Diseases.” The corresponding authors include Friend as well as Rong Chen and Eric Schadt from the Icahn Institute. Interested in the Resilience Project? You can sign up online for updates. “We will let you know when we’re accepting volunteers to join the search,” the organizers say.