Did You Inherit a Childhood Disease That You Unknowingly Conquered?

New Scientist
Stories from New Scientist.
Aug. 3 2014 7:08 AM

Unexpected Genetic Heroes

Did you inherit a childhood disease that you somehow conquered?

A swab from the mouth of a man as part of a DNA test.
One cheek swab for DNA could determine whether you’re an unexpected hero.

Photo by Jung Yeon-Je/AFP/Getty Images

Biologist Stephen Friend is president and co-founder of the nonprofit research organization Sage Bionetworks in Seattle, and co-director of the Resilience Project, which starts in September He is searching for exceptional people who carry genes for serious childhood disease but have never gotten sick—are you one of them?

Why do you want to find people who have genes for serious diseases?
We aim to find relatively healthy adults who have somehow escaped having the classical symptoms, because although they carry the faulty gene that would normally mean they get the disease, they also have something else protecting them—possibly another mutation. We know people who have made it to adulthood without any symptoms are going to be very rare. That’s why we are referring to them as unexpected heroes.

How do you know these people are out there?
My partner in this project Eric Schadt, a genomics professor at Mount Sinai Hospital in New York, has seen examples. One was a woman in her 50s with a mutation in the gene that causes cystic fibrosis but who has never had anything more than mild respiratory problems. And there was a 45-year-old man who never had any symptoms but learned by chance that he had the usually fatal neurological condition Louis-Bar syndrome, which is caused by a faulty gene. Both had an inherited childhood disease but no symptoms. That is exactly what we are looking for.

Advertisement

How will you find these resilient people?
We are asking people to volunteer their DNA in a systematic worldwide search, looking at the vast majority of inherited childhood diseases—from cystic fibrosis to Rett syndrome.

Why is finding them so important?
We know that those who avoided getting sick when young may harbor protective genes. The assumption is that finding these protective factors is a very direct path to developing new therapies.

That’s because almost all of the genetic alterations that cause disease are due to a loss of function, say in a protein that the faulty gene codes for. Equally, a loss of function caused by the second mutations our unexpected heroes carry is probably what’s providing protection. The vast majority of drugs we have use small molecules, which are extremely poor at restoring function, but very good at disrupting it. So if you found a dozen of these protective factors, there is a high chance you could build drugs to mimic most of them by recreating the loss of function.

Who can take part in the project?
Anyone who is over 30 and was relatively healthy in childhood—who did not go to a doctor with a severe illness—can volunteer. None of the hundreds of inherited diseases we are considering would be a minor bother.

How can people contribute their genetic information?
You sign up and give consent on our website resilienceproject.me—you can register interest in taking part now. We will send out a cotton swab that you scrape inside your cheek to pick up enough cells to allow your DNA to be analyzed. You mail it in, and we test for the 125 childhood diseases we’re focused on—those that are very severe, where you are highly likely to suffer the full illness if you have the mutated gene. After we test your sample, you are most likely to get a card saying that we don’t see any evidence that you are an unexpected hero. Or it may say we think it is worth doing further analysis to validate something we found.

We hope to find a million people to take part, and among them, the handful of people who are likely to fit the unexpected hero criteria.

What will you do when you find this handful of people?
To see if we can find their resilience factors, we would want to look deeply at their whole genome and other aspects of their biology that might provide clues, such as their RNA, proteins, and metabolism.

  Slate Plus
Slate Picks
Dec. 19 2014 4:15 PM What Happened at Slate This Week? Staff writer Lily Hay Newman shares what stories intrigued her at the magazine this week.