With a deluge of DNA sequences pouring in from various studies, researchers diving in are finding that Mendelian genetics may be a lot muddier than expected. Wrinkled peas aside, certain bad mutations may not always be bad.

After sifting through the genetic codes of nearly 600,000 adults, researchers discovered that 13 of them were healthy despite carrying mutations that were thought to guarantee devastating childhood disorders, such as cystic fibrosis and those that cause severe skeletal malformations. The authors, led by Stephen Friend of the Icahn School of Medicine at Mount Sinai in New York, hypothesize that these 13 apparently normal adults have other genetic elements that compensate or buffer the effects of those mutations. If that’s true and researchers can pinpoint the source of their genetic resilience, the findings may offer critical information about how to cure these diseases in the not so genetically lucky, the authors report in Nature Biotechnology.

Most research in the past has focused on finding the cause of a disease, Friend said in a teleconference with media. But, he added, “finding the gene that is causing the disease is not the same as trying to find a way to prevent those symptoms.” A few years ago, he and a colleague came up with the idea of looking for cures not in the sick, but in people who should have gotten sick—people who look healthy and normal.

As a proof-of-concept, the researchers set out to see if they could find such people. They scanned the genetic codes of 589,306 adults from 12 studies, zeroing in on 874 genes linked to 584 Mendelian childhood disorders—disorders that can be caused by a mutation in a single trait, which would then be inherited according to Mendel’s laws.

The researchers picked disorders that appear in childhood to minimize the risk that the affected individuals have delayed onset, appearing healthy in early adulthood but becoming sick later in life. They also focused on disorders that tend to have very obvious symptoms, such as malformed skulls and blistering skin, to try to ensure that the disease was not simply overlooked. And all of the disease mutations were thought to be completely “penetrant,” meaning that if the mutations were present the disease was considered guaranteed.

At first, the researchers wound up with 15,597 people who seemed to dodge a genetic bullet. But after filtering out poor-quality DNA data and shoddy evidence of complete penetrance, the researchers were left with 13 people who had verifiable mutations thought to guarantee one of eight diseases. The eight diseases were: cystic fibrosis, Smith-Lemli-Opitz syndrome, familial dysautonomia, epidermolysis bullosa simplex, Pfeiffer syndrome, autoimmune polyendocrinopathy syndrome, acampomelic campomelic dysplasia, and atelosteogenesis.

Ideally, the researchers would have gone back to those 13 patients and made sure that there wasn’t some other oddity in their DNA samples or some mistake in their health records that may have hidden their disease. Unfortunately, all of their consent forms did not allow for them to be re-contacted—those 13 may never know of their serendipitous genetics.

The lack of follow-up with the 13 makes the current study’s findings impossible to double-check. More studies will be needed to back up the finding, according to Friend and Daniel MacArthur, a geneticist at Massachusetts General Hospital who was not involved in the study.

In a commentary, MacArthur points out that with only 13 resilient genomes in more than half a million, validating the study will require “incredibly large sample sizes.” And using such studies to find clues for curing disease may be even more difficult.

But, MacArthur adds, as scientists around the world work to assemble massive databases of hundreds of millions of human genomes, it’s already clear that we have a lot to learn about disease genetics. “The results highlight our incomplete understanding of the penetrance of most human diseases, a message that has been consistent from other large-scale variation studies but never documented at this scale and in such severe disease phenotypes.”

Nature Biotechnology, 2015. DOI: 10.1038/nbt.3514 (About DOIs).