It's hard to find a needle in a haystack—but it's a lot easier if you make the haystack a lot smaller. That's the principle behind a faster, more efficient method for finding disease-causing genes being pioneered by UW researchers.
Last December, the team, led by Michael Bamshad, professor of pediatrics and genome sciences, and Jay Shendure, assistant professor of genome sciences, announced that they had identified the gene involved in Miller syndrome, a rare hereditary condition that causes facial and limb deformities.
"We had in the past used more traditional approaches to look for the Miller syndrome gene but failed," says Bamshad. "So we were very interested in learning whether we could use a new strategy based on the sequencing of exomes to find it."
The exome is the portion of a person's genetic material that codes for proteins. The entire set of genetic material, called the genome, contains a huge number of genetic building blocks. But the exome, which represents about 1 percent of the genome, is merely large. By sequencing the exomes of four people with Miller syndrome, and comparing them with sequences from eight unaffected individuals, the research team was able to quickly zero in on the culprit gene.
Exome sequencing is likely to be particularly powerful in identifying genes involved in diseases, like Miller syndrome, that involve mutations in a single gene. Bamshad and Shendure, along with Deborah Nickerson, professor of genome sciences, are now using exome sequencing to look for the genes involved in other disorders of this type. "There will likely be many more success stories such as this over the next several years," Bamshad predicts.