Navigation Links
Genes and their regulatory 'tags' conspire to promote rheumatoid arthritis
Date:1/20/2013

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."


'/>"/>
Contact: Catherine Kolf
ckolf@alumni.nd.edu
443-287-2251
Johns Hopkins Medicine
Source:Eurekalert  

Related medicine news :

1. Hepatitis B virus promotes oncogenesis through microRNA modulation
2. Cancer Genome Institute at Fox Chase among first to offer clinical blueprint of cancer genes
3. Induction of adult cortical neurogenesis by an antidepressant
4. Genes Changes Seen in Alzheimers Can Be Found in Infancy: Study
5. Bacterial imbalance contributes to intestinal inflammation and carcinogenesis
6. Genes Linked to Effectiveness of Tamoxifen for Breast Cancer
7. Genes Linked to Autism Seem to Have Strong Tendency to Mutate
8. Scientists Now See 200 Genes Linked to Crohns Disease
9. Genes May Influence Effectiveness of Anti-Smoking Policies
10. Ethiopians and Tibetans thrive in thin air using similar physiology, but different genes
11. Valuable tool for predicting pain genes in people
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Genes and their regulatory 'tags' conspire to promote rheumatoid arthritis
(Date:12/6/2016)... , ... December 06, 2016 ... ... on Friday, November 25th, when SevenPoint2 released the much-anticipated HydroFX for Water®. ... eye-catching label design. Featuring one of the world’s most powerful antioxidants, molecular ...
(Date:12/6/2016)... ... December 06, 2016 , ... TopConsumerReviews.com recently gave a ... Scooters . , Mobility Scooters give freedom to people who need help getting around. ... may be facing a long period of rehabilitation after an illness or accident. There ...
(Date:12/5/2016)... ... December 05, 2016 , ... "FCPX Overlay Glare is a ... lighting effect without heavy rendering or complicated compositing," said Christina Austin - CEO of ... create an organic spectrum of lights that simulates the look of a glare. ...
(Date:12/5/2016)... GA (PRWEB) , ... December ... ... technology and security executive networking and relationship-marketing firm, announced today that nominations ... the 2017 Information Security Executive® (ISE®) Central Awards. , Awards include the ...
(Date:12/5/2016)... ... December 05, 2016 , ... Physicians Education ... Annual International Congress on Hematologic Malignancies®: Focus on Leukemias, Lymphomas, and Myeloma, on ... “We are honored to have Amy E. Herman present at this year’s conference, ...
Breaking Medicine News(10 mins):
(Date:12/5/2016)... , Dec. 5, 2016   Lexicon Pharmaceuticals, ... results today from a Phase 2 clinical study of ... Lexicon in collaboration with JDRF, the leading global organization ... of this Phase 2 clinical trial, which randomized a ... of a once-daily 400 mg dose of sotagliflozin compared ...
(Date:12/5/2016)... , December 5, 2016 According to ... Treatment modalities (Chondrocyte Transplantation, Growth Factor Technology, Tissue Scaffolds, Cell-free composites), ... by MarketsandMarkets, the market is projected to reach USD 779.8 Million ... CAGR of 13.5% during the forecast period of 2016 to 2021. ... ...
(Date:12/5/2016)... PORTLAND, Oregon and PUNE, India ... a new report by Allied Market Research, titled, "Global Cancer ... the global revenue of cancer biomarkers market is projected to ... at a CAGR of 13.3% from 2016 to 2022. Omic ... share in 2015 and is expected to maintain its dominance ...
Breaking Medicine Technology: