A new online database combining symptoms, family history and genetic sequencing information is speeding the search for diseases caused by a single rogue gene. As described in an article in the May issue of Human Mutation, the database, known as PhenoDB, enables any clinician to document cases of unusual genetic diseases for analysis by researchers at the Johns Hopkins University School of Medicine or the Baylor College of Medicine in Houston.
If a review committee agrees that the patient may indeed have a previously unknown genetic disease, the patient and some of his or her family members may be offered free comprehensive genetic testing in an effort to identify the disease culprit.
"PhenoDB is much more useful than I even thought it would be," says Ada Hamosh, M.D., M.P.H., a professor in the McKusick-Nathans Institute of Genetic Medicine at the Johns Hopkins University School of Medicine. "Bringing all of this information together is crucial to figuring out what our genetic variations mean." The database is designed to capture a bevy of standardized information about phenotype, which Hamosh defines as "any characteristic of a person" — symptoms, personal and family health history, appearance, etc.
Hamosh and others developed PhenoDB for the Baylor-Hopkins Center for Mendelian Genomics (BHCMG), a four-year initiative that, together with its counterparts at Yale University and the University of Washington, is charged with uncovering the genetic roots of every disorder caused by a single faulty gene. There are an estimated 3,000 inherited disorders that have been described phenotypically in scientific papers but whose genetic causes have not yet been pinpointed, Hamosh says, but since many single-gene disorders are extremely rare, she suspects that many more have not yet made it into the literature.
The Centers for Mendelian Genomics have a powerful tool at their disposal, known as whole-exome sequencing. Just a few years ago, Hamosh explains, a geneticist trying to diagnose the cause of an inherited disease would have made an educated guess based on the patient's signs and symptoms about which gene might be at fault, and ordered a test of that gene. If the test came back negative for a mutation, she would order a test of a different gene, and so on. But whole-exome sequencing, in which about 90% of a person's genes are sequenced at one time, has been growing steadily cheaper, and it is this tool that the Centers will use to capture genetic sequencing information (whole-genome sequencing is the next step, but it remains too expensive for many uses, Hamosh notes, as it includes all of a person's DNA, most of which contains no genes).
However, making sense of the deluge of data yielded by whole-exome sequencing presents its own challenges. "The average person has tens of thousands of variations from the standard genetic sequence," Hamosh explains, "and we don't know what most of those variations mean." To parse these variations, she says, "one of the things that needs to change is that the lab doing the testing needs to have the whole phenotype, from head to toe." Researchers will then be better equipped to figure out which variations may or may not be relevant to a patient's illness. Another advantage of the database is that it enables colleagues at distant locations — such as Baylor and Johns Hopkins — to securely access the information and collaborate. Hamosh notes that the database enables different users to be afforded different levels of access — for example, a health provider will only be able to see the information he or she has entered — and that information is deidentified to protect patient privacy. In addition, providers must have patients' consent to be included in PhenoDB.
PhenoDB would be useful for any research project that seeks to match genomic information with its phenotypic effects, Hamosh says, and with that in mind, the Baylor-Hopkins Center for Mendelian Genomics has made the PhenoDB software available for free download at http://phenodb.net. She predicts that similar tools will soon be incorporated into electronic health records as well, so that "doctors will have patients' genomic information at their fingertips and can combine that with information about health history, disease symptoms and social situation to practice truly individualized medicine."
Other authors on the paper are Nara Sobreira, Julie Hoover-Fong, Corinne Boehm and David Valle, all of the Johns Hopkins University School of Medicine; V. Reid Sutton of Baylor College of Medicine; and François Schiettecatte of FS Consulting.
The Baylor-Hopkins Center for Mendelian Genomics is funded by the National Human Genome Research Institute (grant number 1U54HG006542).
Link to the paper: http://onlinelibrary.wiley.com/doi/10.1002/humu.22283/abstract
Shawna Williams | EurekAlert!
MRI contrast agent locates and distinguishes aggressive from slow-growing breast cancer
25.09.2017 | Case Western Reserve University
Investigators may unlock mystery of how staph cells dodge the body's immune system
22.09.2017 | Cedars-Sinai Medical Center
Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.
A warming planet
Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.
The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...
Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!
When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...
For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.
Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...
19.09.2017 | Event News
12.09.2017 | Event News
06.09.2017 | Event News
25.09.2017 | Physics and Astronomy
25.09.2017 | Life Sciences
25.09.2017 | Physics and Astronomy