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New ‘Deep Sequencing’ Technique Detects Mutations Missed By Other Methods

By John Lugo featured image Maggie Bartlett, NHGRI

A new “deep sequencing” approach to patient treatment can discover disease-related mutations that other genome sequencing methods may miss.

Scientists have used this technique, known as “targeted high-coverage sequencing,” to identify somatic mutations in patients who have brain disorders. These mutations may affect only a portion of cells, which may make them difficult to find.

The technique reads DNA fragments at least 200 times, much more than the typical 30 of a regular sequence. A study that included 158 patients discovered 27 mutations that affected brain function, and eight of those mutations were in just a portion of blood cells.

“Our study creates a paradigm shift, providing evidence that a significant proportion of mutations causing brain disorders occur after conception and would be missed by routine testing,” says Saumya Jamuar, a clinical geneticist at the KK Women’s and Children’s Hospital in Singapore who helped conduct the study.

Christopher Walsh, chief of genetics and genomics at Boston Children’s Hospital and who also helped conduct the study, says the results also suggest neuropsychiatric disorders may result from mutations that are detectable in as little as 10 percent of blood cells in a patient.