Skip to Content

Studying Extreme Genomes

Tales of human outliers, including an unbreakable man who inspired new treatments for osteoporosis.

In the late 1990s, a surprised radiologist in Connecticut came across a real-life version of Bruce Willis’s character in the movie Unbreakable. The patient came to the hospital after a motor vehicle accident. But rather than revealing broken bones, the x-rays revealed an extremely high bone density. (Bone-density testing later confirmed it to be the highest ever recorded.) In 2002, Richard Lifton, a geneticist at Yale who specializes in genetic analysis of human outliers–people with extreme phenotypes–discovered that a mutation in a gene called LDL-related receptor protein 5 was responsible for the man’s high bone density, a condition shared by about half of his family. (While mutations in this gene can sometimes lead to health problems, Lifton says that this family’s only complaint was that they couldn’t float in water because their bones are so dense.)

Lifton’s team went on to study the molecular pathway affected by this mutation–and just seven years later, drugs targeting one of these molecules is in late-stage clinical testing for osteoporosis, a progressive disease of brittle bones that leads to fracture and a substantially increased risk of disability and death among the elderly.

While the unbreakable man’s case is unusual, Lifton’s approach isn’t. Anyone familiar with the history of human genetics knows that many of the field’s most significant early discoveries came from studies of families afflicted with rare diseases. Uncovering the genes involved in those diseases has in turn shed light on more common medical problems, such as high cholesterol, Parkinson’s disease, and autism.

As genetic technologies have improved, so has the scope of these investigations. While researchers once had to undertake painstaking pedigree studies to pinpoint the region of the genome affected in a particular family and then sift through the most likely genetic candidates in that region, rapid advances in DNA sequencing in the past few years have significantly broadened the number of genes that can be searched. Scientists are now beginning to sequence individuals’ entire exome–the gene coding region of the genome–searching for mutations in genes never suspected to play a role in particular diseases. Lifton, whose research has focused in large part on the genetics of hypertension, is now sequencing the exomes of a number of people referred to his clinic with severe early hypertension. Expect to see a growing number of studies along these lines.

Keep Reading

Most Popular

individual aging affects covid outcomes concept
individual aging affects covid outcomes concept

Anti-aging drugs are being tested as a way to treat covid

Drugs that rejuvenate our immune systems and make us biologically younger could help protect us from the disease’s worst effects.

Europe's AI Act concept
Europe's AI Act concept

A quick guide to the most important AI law you’ve never heard of

The European Union is planning new legislation aimed at curbing the worst harms associated with artificial intelligence.

Uber Autonomous Vehicles parked in a lot
Uber Autonomous Vehicles parked in a lot

It will soon be easy for self-driving cars to hide in plain sight. We shouldn’t let them.

If they ever hit our roads for real, other drivers need to know exactly what they are.

crypto winter concept
crypto winter concept

Crypto is weathering a bitter storm. Some still hold on for dear life.

When a cryptocurrency’s value is theoretical, what happens if people quit believing?

Stay connected

Illustration by Rose WongIllustration by Rose Wong

Get the latest updates from
MIT Technology Review

Discover special offers, top stories, upcoming events, and more.

Thank you for submitting your email!

Explore more newsletters

It looks like something went wrong.

We’re having trouble saving your preferences. Try refreshing this page and updating them one more time. If you continue to get this message, reach out to us at customer-service@technologyreview.com with a list of newsletters you’d like to receive.