For the first time, scientists have successfully used a method called exome sequencing to quickly discover a previously unknown gene responsible for a mendelian disorder.
While most mendelian disorders are rare, there are 7,000-plus suspected mendelian disorders that in aggregate affect millions of people in the United States, according to Dr. Michael J. Bamshad, one of the senior authors of the study, a UW professor of genome sciences and pediatrics, and a pediatrician at Seattle Children's. "Our results show that scientists could use exome sequencing to identify the genetic cause for thousands of disorders for which the gene hasn't been discovered."
"One of the reasons that this strategy is so powerful is that the scientists need only use a small number of unrelated cases to find the gene," said the other senior author of the study, Dr. Jay Shendure, UW assistant professor of genome sciences.
Dr. James Kiley, director of the Division of Lung Diseases at the National Heart, Lung and Blood Institute, part of the National Institutes of Healths in Bethesda, Md., said, "Following the recent successes with genome-wide association studies, this promising technology will advance our understanding of the genetic variants of both common disorders and rare diseases."
The disorder the UW research team used to test the strategy is Miller syndrome, whose genetic cause had been impossible to determine through conventional approaches. People with this syndrome have a number of malformations affecting their mouths, eyelids, ears, and feet. The research team was able to find that mutations in the gene, DHODH, cause Miller syndrome.
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."
The study published in Nature Genetics was a collaborative effort among scientists from many disciplines and institutions. Other authors include co-first author Kati J. Buckingham, from the UW Department of Pediatrics; Choli Lee, UW Department of Genome Sciences; Abigail W. Bigham, UW Department of Pediatrics; Holly K. Tabor, UW Department of Pediatrics and the Treuman Center for Pediatric Bioethics at Seattle Children's; Karin M. Dent and Chad D. Huff from the University of Utah departments of pediatrics and human genetics, respectively; Paul T. Shannon of the Institute of Systems Biology in Seattle; Ethylin Wang Jabs of the Department of Genetics and Genome Sciences at Mount Sinai School of Medicine and the Department of Pediatrics at Johns Hopkins University, and Deborah Nickerson from the UW Department of Genome Sciences.
The research was funded by grants from the Eunice Kennedy Shriver National Institute of Child Health and Health and Human Development, the National Human Genome Research Institute, and the Heart, Lung, and Blood Institute, all at the National Institutes of Health; the state of Washington Life Sciences Discovery Fund and the Washington Research Foundation.
Leila Gray | EurekAlert!
Closing in on advanced prostate cancer
13.12.2017 | Institute for Research in Biomedicine (IRB Barcelona)
Visualizing single molecules in whole cells with a new spin
13.12.2017 | Wyss Institute for Biologically Inspired Engineering at Harvard
MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.
Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...
Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...
Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.
To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...
The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.
Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...
With innovative experiments, researchers at the Helmholtz-Zentrums Geesthacht and the Technical University Hamburg unravel why tiny metallic structures are extremely strong
Light-weight and simultaneously strong – porous metallic nanomaterials promise interesting applications as, for instance, for future aeroplanes with enhanced...
11.12.2017 | Event News
08.12.2017 | Event News
07.12.2017 | Event News
13.12.2017 | Health and Medicine
13.12.2017 | Physics and Astronomy
13.12.2017 | Life Sciences