SUPERHEROES with powers that come from mutations in their genomes are, like the X-Men, a staple of comic books and movies. Now an extensive study of the genetics of more than 500,000 people has revealed a different kind of mutant superhero: a small number of individuals who seem to be perfectly healthy despite carrying in their DNA a mutation linked to a severe childhood disorder.

The 13 adults identified were found to have faulty genes associated with one of eight different inherited conditions. These included cystic fibrosis, a disease that interferes with breathing, and atelosteogenesis, which affects bone and limb development. People with the eight different genetic faults can die at birth or shortly after.

Eric Schadt of the Icahn School of Medicine at Mount Sinai, New York, and Stephen Friend of Sage Bionetworks, a non-profit organisation based in Seattle that promotes open science, began their investigation by collecting genetic data from 12 studies carried out by other groups. The data, from European, Asian and American sources that included 23andMe, a biotechnology company, and the Beijing Genomics Institute, yielded an initial pool of DNA sequences from 589,306 people. Of these, full genome sequences were only available for 3,524 individuals. The remainder of the data came from medical screens that identified mutations in a selection of genes, or from exome studies that only looked at the genes that code for proteins—about 1% of the total.

Dr Schadt, Dr Friend and their colleagues then winnowed these down by selecting sequences containing mutations known to cause severe diseases in childhood. They focused on Mendelian disorders, diseases caused by a mutation in a single gene and named after Gregor Mendel, an Augustinian friar who founded modern genetics. The researchers chose only mutations that were believed always to result in the individual developing the disease. That took the number down to 15,597 people, each carrying at least one mutation for one of 163 different diseases.

Next, they checked the sequences and discarded any that they suspected may have contained errors. They also excluded those carrying mutations that occurred in more than 0.5% of the population: relatively common mutations are unlikely to result in severe forms of a disease. That left 303 candidates whose sequences and medical records were scrutinised to ensure that the individuals concerned were healthy and that the mutations they carried had been identified in the scientific literature as giving rise to a disease that would be likely to prevent them surviving to adulthood. The research team also obtained original biological samples, where possible, to verify the DNA sequences.

At that point, as the team report in Nature Biotechnology, they were left with just 13 people whose medical records indicated they were healthy, despite carrying a mutation for one of the eight severe diseases. Unfortunately, only partial DNA sequences were available for the 13. Ideally, the next step would be to sequence these individuals’ entire genomes to discover why they were able to carry, with seemingly no ill-effects, mutations that are deadly in others. Any genes thought to confer protection could be spliced into the genomes of diseased cells grown in a laboratory to test their effects. Such work might provide a step towards the discovery of new treatments. Frustratingly, the researchers could not do that because the consent forms used by the subjects did not provide permission for them to be recontacted.

The team, however, have not given up on identifying genetic superheroes and finding out what accounts for their ability to resist inherited diseases. Together with Jason Bobe, also of the Icahn School of Medicine, they have launched the Resilience Project. The idea is cheaply to screen the DNA of well over 100,000 healthy people for a wide range of genetic disorders. This time, the consent forms will allow the researchers to recontact any potential survivors so that their genomes can be fully sequenced. Such folk may not have the ability to take on comic-book villains, but have an even more extraordinary power fortuitously hidden in their genes.