"Identifying the genetic basis of rare, single-gene diseases is of substantial interest to medical scientists," said Sarah Ng, a UW genome sciences graduate student and co-first author of the study, "because it provides important knowledge about disease mechanisms, biological pathways, and potential targets for therapies."

"Once we discover the causative gene," she added, "we can begin to look at how the gene might lead to the development of disease and what factors predict the outcome."

After scientists identify one causative gene and its repercussions, by extension they might discover other genes or environmental agents that affect the same biological pathway. For example, the malformation patterns found in Miller syndrome are similar to the birth defects in fetuses of some, but not all, mothers who took the drug methotrexate during pregnancy. Knowing this might provide some clues to genetic susceptibility to birth defects from methotrexate.

The ability of exome sequencing to identify a causative gene in a few months, compared to earlier methods that took years, "caused an audible gasp in the audience when we presented these findings to our peers," Bamshad said. "The power of this strategy is remarkable to many of us."

"We hope that the results of this study help point the way for thousands of scientists working on rare disorders who are seeking more efficient ways to locate the causative gene," Shendure added. "The exome sequencing strategy may also prove useful in studies of common disorders with complex genetics."

Source: University of Washington