Everyone has heard about genetic mutations causing serious disease. Finding one in your genome was like getting a death sentence. Recently, however, geneticists have been surprised that many people with these mutations don’t ever get sick.
You’re probably among them. “Lurking in the genes of the average person are about 54 mutations that look as if they should sicken or even kill their bearer,” says Erica Check Hayden in Nature. “But they don’t.” [Emphasis added.] And therein lies a scientific revolution. The growing realization that humans survive these mutations is leading to “a radical revision of human genetics,” she says.
Few would have thought to ask such a question in years past, but medical genetics has been going through a bit of soul-searching. The fast pace of genomic research since the start of the twenty-first century has packed the literature with thousands of gene mutations associated with disease and disability. Many such associations are solid, but scores of mutations once suggested to be dangerous or even lethal are turning out to be innocuous. These sheep in wolves’ clothing are being unmasked thanks to one of the largest genetics studies ever conducted: the Exome Aggregation Consortium, or ExAC.
We mentioned ExAC before, noting that a billion genes have failed to turn up any beneficial mutations. This time we look at the flip side; are “harmful” mutations really as deadly as we thought?
Part of the misdiagnosis problem came from a common statistical error, illustrated by an old joke: “Monday, Joe got drunk on gin and soda water. Tuesday, Joe got drunk on bourbon and soda water. Wednesday, Joe got drunk on vodka and soda water. Conclusion: soda water causes drunkenness.” The mistake could have been prevented by comparing Joe to people who drank soda water alone or added it to non-alcoholic drinks.
Similarly, doctors and scientists can find a genetic variant in several individuals with fatal genetic diseases and rush to the conclusion that the common gene was the cause of the disease, before checking to see how widespread the variant is in the general population. Philosophers use illustrations like this to teach rules of logical inference.
The error can be forgiven in this case. Before now, scientists lacked enough data to compare genomes. ExAC is changing that. It’s a welcome development. The editors of Nature want to accelerate the correction:
