Over the past few years, teams of scientists have been finding genetic glitches related to a wide variety of disorders by sequencing exomes, the protein-coding portions of the genome. But these genetic tests are typically out of reach for people unless they enroll in research studies, and even then, they’re almost never privy to their individual results.
But that looks set to change: A few clinics are debuting large programs that rely on sequencing of exomes or even of whole genomes, and making the results directly available to individuals. For less than $10,000 each, the tests offer people with unexplained genetic disorders the chance to find the cause of their condition.
The first academic lab to offer clinical exome sequencing was the Whole Genome Laboratory at Baylor College of Medicine in Houston. Since November 2011, the lab has sequenced the exomes of some 1,700 individuals with undiagnosed conditions, including many children with developmental disorders. It now averages about 200 exomes a month.
"It's gone gangbusters," says Richard Gibbs, director of Baylor's Human Genome Sequencing Center, which helped establish the new lab. The researchers have pinpointed the genetic cause of about one-quarter of the 1,700 cases as mutations in known disease genes, he says.
Last week, the Harvard-affiliated Partners Healthcare Center in Boston launched a similar lab focused on sequencing whole genomes. And two private companies — Ambry Genetics in Aliso Viejo, California, and GeneDx in Gaithersburg, Maryland — have offered clinical exome sequencing since 2011.
Deciding which parts of the sequencing data should be divulged to individuals is far from straightforward. A few mutations are clearly associated with disease, but most are still tricky to interpret.
From a research perspective, however, the development is unequivocally exciting, experts say.
That's because at clinics affiliated with academic institutions, participants may choose to contribute their de-identified data into freely available databases that researchers can tap for their studies. That could prove a huge advantage for researchers funded by agencies such as the National Institutes of Health (NIH).
"A ton more samples can be screened in the clinic than can be screened in NIH-funded studies," says Jonathan Sebat, associate professor of psychiatry at the University of California, San Diego. "That's ultimately what's going to drive discovery forward."
Many clinical tests already exist for undiagnosed developmental disorders. These tests typically screen a single gene or a panel of genes for certain rare variants, which appear only in a few people, or common variants, which crop up in at least five percent of the general population.