Forum für Wissenschaft, Industrie und Wirtschaft

Hauptsponsoren:     3M 
Datenbankrecherche:

 

Genes and their regulatory 'tags' conspire to promote rheumatoid arthritis

21.01.2013
Johns Hopkins scientists identify epigenetic changes that referee genetic risk

In one of the first genome-wide studies to hunt for both genes and their regulatory "tags" in patients suffering from a common disease, researchers have found a clear role for the tags in mediating genetic risk for rheumatoid arthritis (RA), an immune disorder that afflicts an estimated 1.5 million American adults.

By teasing apart the tagging events that result from RA from those that help cause it, the scientists say they were able to spot tagged DNA sequences that may be important for the development of RA. And they suspect their experimental method can be applied to predict similar risk factors for other common, noninfectious diseases, like type II diabetes and heart ailments.

In a report published in Nature Biotechnology Jan. 20, the researchers at Johns Hopkins and the Karolinska Institutet say their study bridges the gap between whole-genome genetic sequencing and diseases that have no single or direct genetic cause. Most genetic changes associated with disease do not occur in protein-coding regions of DNA, but in their regulatory regions, explains Andrew Feinberg, M.D., M.P.H., a Gilman scholar, professor of molecular medicine and director of the Center for Epigenetics at the Johns Hopkins University School of Medicine's Institute for Basic Biomedical Sciences. "Our study analyzed both and shows how genetics and epigenetics can work together to cause disease," he says.

Rheumatoid arthritis is a debilitating disease that causes inflammation, stiffness, pain and disfigurement in joints, especially the small joints of the hands and feet. It is thought to be an autoimmune disease, meaning that the body's immune system attacks its own tissues, an assault led primarily by white blood cells. According to Feinberg, several DNA mutations are known to confer risk for RA, but there seem to be additional factors that suppress or enhance that risk. One probable factor involves chemical "tags" that attach to DNA sequences, part of a so-called epigenetic system that helps regulate when and how DNA sequences are "read," how they're used to create proteins and how they affect the onset or progress of disease.

To complicate matters, Feinberg notes, the attachment of the tags to particular DNA sequences can itself be regulated by genes. "The details of what causes a particular sequence to be tagged are unclear, but it seems that some tagging events depend on certain DNA sequences. In other words, those tagging events are under genetic control," he says. Other tagging events, however, seem to depend on cellular processes and environmental changes, some of which could be the result, rather than the cause, of disease.

To tease apart these two types of tagging events, the researchers catalogued DNA sequences and their tagging patterns in the white blood cells of more than 300 people with and without one form of RA.

The team then began filtering out the tags that did not appear to affect RA risk. For example, if tags were seen on the same DNA sequence in those with and without RA, it was assumed that the tags at those sites were irrelevant to the cause or development of the disease. Then, from among the RA-relevant tags, they narrowed in on tags whose placement seemed to be dependent on DNA sequence. Finally, they made sure that the DNA sequences identified were themselves more prevalent in patients with RA. In this way, they created a list of DNA sequences associated with altered DNA tagging patterns, both of which were associated with RA.

Ultimately, the team identified 10 DNA sites that were tagged differently in RA patients and whose tagging seemed to affect risk for RA. Nine of the 10 sites were within a region of the genome known to play an important role in autoimmune diseases, while the 10th was on a gene that had never before been associated with the disease. "Since RA is a disease in which the body's immune system turns on itself, current treatments often involve suppressing the entire immune system, which can have serious side effects," Feinberg says. "The results of this study may allow clinicians to instead directly target the culpable genes and/or their tags."

"Our method allows us to predict which tagging sites are most important in the development of a disease. In this study, we looked for tagging sites under genetic control, but similar tags can be triggered by environmental exposures, like smoking, so there are many applications for this type of work," says Yun Liu, Ph.D., a lead researcher on the project.

The study also may shed light on how evolution works, explains Feinberg. "It seems that natural selection might not simply be selecting for an individual's current fitness level but also for the adaptability of future generations given an unknown future. We think that certain genetic sequences may be biologically beneficial and conserved over time because they increase the amount of variation found in tagging patterns, giving individuals a greater chance of adapting to environmental changes."

Other authors of the report include Martin J. Aryee, M. Daniele Fallin, Arni Runarsson and Margaret Taub of the Johns Hopkins University School of Medicine; and Leonid Padyukov, Espen Hesselberg, Lovisa Reinius, Nathalie Acevedo, Marcus Ronninger, Lementy Shchetynsky, Annika Scheynius, Juha Kere, Lars Alfredsson, Lars Klareskog and Tomas J. Ekström of the Karolinska Institutet, Sweden.

This work was supported by grants from the National Institutes of Health's Centers of Excellence in Genomic Science (5P50HG003233), the Swedish Research Council, the Swedish COMBINE project, the Swedish Foundation for Strategic Research, AFA Insurance and the European Research Council.

ON THE WEB:

Feinberg Lab: http://epigenetics.jhu.edu/

Feinberg's Profile: http://epigenetics.jhu.edu/?section=personnelPages&personID=2

Catherine Kolf | EurekAlert!
Further information:
http://www.jhu.edu/

More articles from Health and Medicine:

nachricht New leukemia treatment offers hope
23.09.2016 | King Abdullah University of Science and Technology

nachricht Alzheimer’s: Cellular Mechanism Provides Explanation Model for Declining Memory Performance
21.09.2016 | Deutsches Zentrum für Neurodegenerative Erkrankungen e.V. (DZNE)

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Synthese-chemischer Meilenstein: Neues Ferrocenium-Molekül entdeckt

Wissenschaftler der Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) haben zusammen mit Kollegen der Freien Universität Berlin ein neues Molekül entdeckt: Die Eisenverbindung in der seltenen Oxidationsstufe +4 gehört zu den Ferrocenen und ist äußerst schwierig zu synthetisieren.

Metallocene werden umgangssprachlich auch als Sandwichverbindungen bezeichnet. Sie bestehen aus zwei organischen ringförmigen Verbindungen, den...

Im Focus: Neue Entwicklungen in der Asphären-Messtechnik

Kompetenzzentrum Ultrapräzise Oberflächenbearbeitung (CC UPOB) lädt zum Expertentreffen im März 2017 ein

Ob in Weltraumteleskopen, deren Optiken trotz großer Abmessungen nanometergenau gefertigt sein müssen, in Handykameras oder in Endoskopen − Asphären kommen in...

Im Focus: Mit OLED Mikrodisplays in Datenbrillen zur verbesserten Mensch-Maschine-Interaktion

Das Fraunhofer-Institut für Organische Elektronik, Elektronenstrahl- und Plasmatechnik FEP arbeitet seit Jahren an verschiedenen Entwicklungen zu OLED-Mikrodisplays, die auf organischen Halbleitern basieren. Durch die Integration einer Bildsensorfunktion direkt im Mikrodisplay, lässt sich u.a. die Augenbewegung in Datenbrillen aufnehmen und zur Steuerung von Display-Inhalten nutzen. Das verbesserte Konzept wird erstmals auf der Augmented World Expo Europe (AWE), vom 18. – 19. Oktober 2016, in Berlin, Stand B25 vorgestellt.

„Augmented Reality“ (erweiterte Realität) und „Wearable Displays“ (tragbare Displays) sind Schlagworte, denen man mittlerweile fast täglich begegnet. Beide...

Im Focus: OLED microdisplays in data glasses for improved human-machine interaction

The Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP has been developing various applications for OLED microdisplays based on organic semiconductors. By integrating the capabilities of an image sensor directly into the microdisplay, eye movements can be recorded by the smart glasses and utilized for guidance and control functions, as one example. The new design will be debuted at Augmented World Expo Europe (AWE) in Berlin at Booth B25, October 18th – 19th.

“Augmented-reality” and “wearables” have become terms we encounter almost daily. Both can make daily life a little simpler and provide valuable assistance for...

Im Focus: Künstliche Intelligenz ermöglicht die Entdeckung neuer Materialien

Mit Methoden der künstlichen Intelligenz haben Chemiker der Universität Basel die Eigenschaften von rund 2 Millionen Kristallen berechnet, die aus vier verschiedenen chemischen Elementen zusammengesetzt sind. Dabei konnten die Forscher 90 bisher unbekannte Kristalle identifizieren, die thermodynamisch stabil sind und als neuartige Werkstoffe in Betracht kommen. Das berichten sie in der Fachzeitschrift «Physical Review Letters».

Elpasolith ist ein glasiges, transparentes, glänzendes und weiches Mineral mit kubischer Kristallstruktur. Erstmals entdeckt im El Paso County (USA), kann man...

Alle Focus-News des Innovations-reports >>>

Anzeige

Anzeige

IHR
JOB & KARRIERE
SERVICE
im innovations-report
in Kooperation mit academics
Veranstaltungen

Einsteins Geburtsstadt wird für eine Woche Hauptstadt der Physik

23.09.2016 | Veranstaltungen

Industrie und Wissenschaft diskutieren künftigen Mobilfunk-Standard 5G auf Tagung in Kassel

23.09.2016 | Veranstaltungen

Fachgespräch Feste Biomasse diskutiert Fragen zum Thema "Qualitätshackschnitzel"

23.09.2016 | Veranstaltungen

 
B2B-VideoLinks
Weitere VideoLinks >>>
Aktuelle Beiträge

Das Korallenthermometer muss neu justiert werden

23.09.2016 | Biowissenschaften Chemie

Doppel-Infektion macht Erreger aggressiver

23.09.2016 | Biowissenschaften Chemie

Synthese-chemischer Meilenstein: Neues Ferrocenium-Molekül entdeckt

23.09.2016 | Biowissenschaften Chemie