Instead of sequencing the whole genome, the CSHL scientists obtained genetic material from two other JBTS patients a mother and daughter and used a powerful genome fractionation method developed at CSHL to sequence just the "exome," the collection of exons, which are the bits of the genome that actually encode proteins. Both approaches yielded the same result: the mutated TMEM216 gene.
"Exons make up just one percent of the genome, so the exome sequencing process is not only much more economical, but also produces results much faster," says Yaniv Erlich, a graduate student in the Hannon laboratory and co-author of the paper. It only took three weeks for the CSHL scientists to find the mutation as compared with many months required by more traditional methods.
Once the causative mutation was identified, the collaborators combined efforts to screen more than 2,700 anonymous participants in the study. This mass screen revealed the high carrier rate of 1:92 among the cohort. The prevalence of the TMEM216 mutation in the wider population remains to be determined.
Whole-exome sequencing has been gaining momentum over the past few years. "But this is one of the first few studies to use next-generation sequencing to identify a causative mutation underlying a rare genetic disease," says Erlich. The CSHL scientists plan to expand their exome sequencing efforts to screen for mutations that cause other rare as well as common genetic diseases.
|Contact: Hema Bashyam|
Cold Spring Harbor Laboratory