Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Genetic sequencing alone doesn't offer a true picture of human disease

24.01.2011
Despite what you might have heard, genetic sequencing alone is not enough to understand human disease. Researchers at Duke University Medical Center have shown that functional tests are absolutely necessary to understand the biological relevance of the results of sequencing studies as they relate to disease, using a suite of diseases known as the ciliopathies which can cause patients to have many different traits.

"Right now the paradigm is to sequence a number of patients and see what may be there in terms of variants," said Nicholas Katsanis, Ph.D. "The key finding of this study says that this approach is important, but not sufficient. If you really want to be able to penetrate, you must have a robust way to test the functional relevance of mutations you find in patients. For a person at risk of type 2 diabetes, schizophrenia or atherosclerosis, getting their genome sequenced is not enough – you have to functionally interpret the data to get a sense of what might happen to the particular patient."

"This is the message to people doing medical genomics," said lead author Erica Davis, Ph.D., Assistant Professor in the Duke Department of Pediatrics, who works in the Duke Center for Human Disease Modeling. "We have to know the extent to which gene variants in question are detrimental – how do they affect individual cells or organs and what is the result on human development or disease? Every patient has his or her own set of genetic variants, and most of these will not be found at sufficient frequency in the general population so that anyone could make a clear medical statement about their case."

Davis, working in the lab of Katsanis, and in collaboration with many ciliopathy labs worldwide, sequenced a gene, TTC21B, known to be a critical component of the primary cilium, an antenna-like projection critical to cell function.

While a few of the mutations could readily be shown to cause two main human disorders, a kidney disease and an asphyxiating thoracic condition, the significance of the majority of DNA variants could not be determined. Davis then tested these variants in a zebrafish model, in which many genes are similar to humans, and showed that TTC21B appears to contribute disease-related mutations to about 5 percent of human ciliopathy cases.

The study, which appears in Nature Genetics online on Jan. 23, shows how genetic variations both can cause ciliopathies and also interact with other disease-causing genes to yield very different sets of patient problems.

Katsanis, the Jean and George Brumley Jr., M.D., Professor of Pediatrics and Cell Biology, and Director of the Duke Center for Human Disease Modeling, is a world expert in ciliopathies such as Bardet-Biedl Syndrome, in which the primary cilium of cells is abnormal and leads to a host of problems. About one child in 1,000 live births will have a ciliopathy, an incidence that is in the range of Down's syndrome, said Katsanis.

"By sequencing genes to identify genetic variation, followed by functional studies with a good experimental model, we can get a much better idea of the architecture of complex, inherited disorders," Katsanis said. "Each individual with a disease is unique," Davis said. "If you can overlay gene sequencing with functional information, then you will be able to increase the fidelity of your findings and it will become more meaningful for patients and families."

It will take more laboratories doing more pointed studies like this one to get a fuller picture of the ciliopathies and other diseases, Davis said.

Katsanis noted that it will take true collaboration within many scientific disciplines as well as scientific finesse to get at the true roots of complex diseases.

"Brute force alone – sequencing – will not help," he said. "Technology is of finite resolution. You must have synthesis of physiology, cell biology, biochemistry and other fields to get true penetration into medically relevant information."

Numerous scientists from other institutions were involved, including those from Johns Hopkins University, University of Pennsylvania, University of Birmingham in the United Kingdom, Universite Louis Pasteur, St. James University Hospital in Leeds, University of Michigan, Baylor College of Medicine, the National Human Genome Research Institute and others.

Funding for the study came from the National Institutes of Health grant from the National Institute of Child Health and Development, other NIH grants, the National Research Service Award (NRSA), a fellowship from the National Institute of Diabetes, Digestive and Kidney disorders, the National Eye Institute the Macular Vision Research Foundation, the Foundation Fighting Blindness, the F.M. Kirby Foundation, the Rosanne Silbermann Foundation, the Polycystic Kidney Disease Foundation, the German Kidney Foundation, the German Research Foundation and a Medical Research Council research training fellowship. This work was also supported in part by the Intramural Research Program of the National Human Genome Research Institute and the Howard Hughes Medical Institute.

Mary Jane Gore | EurekAlert!
Further information:
http://www.duke.edu

More articles from Life Sciences:

nachricht Transport of molecular motors into cilia
28.03.2017 | Aarhus University

nachricht Asian dust providing key nutrients for California's giant sequoias
28.03.2017 | University of California - Riverside

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: A Challenging European Research Project to Develop New Tiny Microscopes

The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.

To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Researchers shoot for success with simulations of laser pulse-material interactions

29.03.2017 | Materials Sciences

Igniting a solar flare in the corona with lower-atmosphere kindling

29.03.2017 | Physics and Astronomy

As sea level rises, much of Honolulu and Waikiki vulnerable to groundwater inundation

29.03.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>