For 10 years, scientists knew that a severe form of microcephaly, an inherited brain malformation, was due to a mutation on chromosome 19. Christopher A. Walsh and other researchers had even narrowed the search for the mutation to a particular stretch of the chromosome. But the section was long and dense, spanning almost 148 genes. The task of identifying a single mutation among those genes was daunting.

“It was staring us in the face for a decade,” says Walsh, an HHMI investigator at Children’s Hospital Boston, “but it was in such a packed area of the genome that no one wanted to go after it.”

Illustration by Dadu Shin