Thirteen Anonymous Genetic Superheroes Walk Among Us – The Atlantic

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It was a reasonable concept, with an encouraging precedent. In 2006, by studying an African-American woman with extremely low cholesterol, scientists identified mutations that dramatically reduce the risk of heart disease by disabling a gene called PCSK9. That discovery led to a new generation of heart drugs. Elsewhere, a Labrador puppy called Ringo was bred with a mutation that causes severe muscular dystrophy, but lived in perfect health thanks to a protective mutation in a different gene. Perhaps Ringo’s resilience will lead to cures for the otherwise untreatable disorder.

Friend’s collaborator Eric Schadt has met a couple of genetic superheroes himself, as Aimee Swartz detailed in The Atlantic two years ago:

“Schadt points to two patients who have come through Mt. Sinai: a woman in her mid-50’s with a mutation in the CFTR gene—the gene understood to cause 100 percent of all cases of cystic fibrosis—who has never had more than mild respiratory issues. And a 45-year-old man who learned during an unrelated medical procedure, that he had Louis–Bar syndrome—a rare neurological disorder caused by a gene mutation—though he had never exhibited any symptoms of the usually fatal disease. “Both carry the code for an inherited childhood disease but do not bear the symptoms of the disease,” he said.

Rather than stumbling across such superheroes, Friend and Schadt wanted to search for them in a systematic way. So they launched an ambitious initiative called the Resilience Project, in which they analyzed the genomes of almost 590,000 people who had taken part in a dozen earlier studies.

They focused on mutations in 874 possible genes that have been linked to a severe childhood disease, and have been described as “completely penetrant”—that is, if you have the mutation, you will inevitably develop the disease. Friend’s team was looking for healthy adults who had somehow dodged these inescapable bullets.

At first, they identified almost 16,000 possible superheroes, who collectively had 300 mutations between them. But in some cases, they weren’t confident that the mutations had been accurately sequenced. In other cases, the mutation turned out to be quite common in the general population, which meant that it couldn’t possibly be the cause of a rare, severe disease. After excluding these uncertain cases, the initial list of 16,000 suspects dropped to just 303.

Thirteen Anonymous Genetic Superheroes Walk Among Us – The Atlantic