Featured Research

from universities, journals, and other organizations

Common disorders: It's not the genes themselves, but how they are controlled

Date:
December 20, 2013
Source:
Case Western Reserve University
Summary:
Many rare disorders are caused by gene mutation. Yet until now, the underlying genetic cause of more common conditions has evaded scientists. New research finds that six common diseases arise from DNA changes located outside genes. The study shows that multiple DNA changes, or variants, work in concert to affect genes, leading to autoimmune diseases.

Many rare disorders are caused by gene mutation, like sickle cell anemia. Yet until now the underlying genetic cause of more common conditions -- for example, rheumatoid arthritis -- has evaded scientists for years.

New research from Case Western Reserve University School of Medicine to appear in the journal Genome Research finds that six common diseases arise from DNA changes located outside genes. The study from the laboratory of Peter Scacheri, PhD, shows that multiple DNA changes, or variants, work in concert to affect genes, leading to autoimmune diseases including rheumatoid arthritis, Crohn's disease, celiac disease, multiple sclerosis, lupus and colitis. Further, for each disease, multiple different genes are manipulated by several small differences in DNA.

"We've known that rare diseases are due to one change within one gene with major effects. The key take away is that common diseases are due to many changes with small effects on a handful of genes," said Scacheri, associate professor of genetics and genome sciences.

The human genome includes 3 billion letters of DNA. Only 1 to 2 percent of the letters are used as the blueprint for proteins, the body's building blocks. Scacheri's team is part of group of scientists investigating where and why DNA goes awry in the remaining 98 percent -- the regions between genes. These regions contain thousands of genetic switches that control the levels of genes. This new finding shows that in common diseases, the fine-tuning of those switches is not quite right, leading to incorrect expression of some key genes -- previously unidentified.

"This is a paradigm shift for the field with respect to pinpointing the genetic causes of common disease susceptibility," Scacheri said.

"The Scacheri lab's study provides a new model for understanding how genetic variants explain variation in common, complex diseases such as rheumatoid arthritis and colitis. That is, the effect of an individual variant may be very small, but when coupled with other nearby variants, the manifestations are much greater, said Anthony Wynshaw-Boris, MD, PhD, chair of the Department of Genetics and Genome Sciences at Case Western Reserve University School of Medicine and University Hospitals Case Medical Center and the James H. Jewell MD '34 Professor of Genetics at the School of Medicine. "This model may also help to explain why genetic studies of these and other common diseases have so far fallen short of providing a satisfactory explanation of the genetic pathways important for the development of these disorders."

The Scacheri laboratory conducted a bioinformatics analysis of new and preexisting data and developed computational tools to identify the switches and genes affected by DNA changes associated with common diseases.

"This is vital information for creating therapies to target these disorders," added Olivia Corradin, a School of Medicine PhD candidate and lead author on the study. "For example, if an individual has a gene that is aberrantly high, he or she will need a medication that will dial it back down. Scientists can't begin to develop a drug to do this without first knowing the gene target and how it needs to be manipulated, either up or down.

Now that the Case Western Reserve team knows the identity of the genes that affect six autoimmune diseases and also understands how the genes are disrupted, the next step is to identify therapies that can restore these genes to their normal levels, so that these diseases can be treated or altogether prevented. In addition, the researchers hope that discovery can lead to improved diagnostic testing for common diseases.


Story Source:

The above story is based on materials provided by Case Western Reserve University. Note: Materials may be edited for content and length.


Journal Reference:

  1. O. Corradin, A. Saiakhova, B. Akhtar-Zaidi, L. Myeroff, J. Willis, R. Cowper-Sal{middle dot}lari, M. Lupien, S. Markowitz, P. C. Scacheri. Combinatorial effects of multiple enhancer variants in linkage disequilibrium dictate levels of gene expression to confer susceptibility to common traits. Genome Research, 2013; DOI: 10.1101/gr.164079.113

Cite This Page:

Case Western Reserve University. "Common disorders: It's not the genes themselves, but how they are controlled." ScienceDaily. ScienceDaily, 20 December 2013. <www.sciencedaily.com/releases/2013/12/131220113207.htm>.
Case Western Reserve University. (2013, December 20). Common disorders: It's not the genes themselves, but how they are controlled. ScienceDaily. Retrieved October 21, 2014 from www.sciencedaily.com/releases/2013/12/131220113207.htm
Case Western Reserve University. "Common disorders: It's not the genes themselves, but how they are controlled." ScienceDaily. www.sciencedaily.com/releases/2013/12/131220113207.htm (accessed October 21, 2014).

Share This



More Health & Medicine News

Tuesday, October 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

CDC Revamps Ebola Guidelines After Criticism

CDC Revamps Ebola Guidelines After Criticism

Newsy (Oct. 21, 2014) The Centers for Disease Control and Prevention have issued new protocols for healthcare workers interacting with Ebola patients. Video provided by Newsy
Powered by NewsLook.com
'Cadaver Dog' Sniffs out Human Remains

'Cadaver Dog' Sniffs out Human Remains

AP (Oct. 21, 2014) Where's a body buried? Buster's nose can often tell you. He's a cadaver dog, specially trained to find human remains and increasingly being used by law enforcement and accepted in courts. These dogs are helping solve even decades-old mysteries. (Oct. 21) Video provided by AP
Powered by NewsLook.com
How Nigeria Beat Its Ebola Outbreak

How Nigeria Beat Its Ebola Outbreak

Newsy (Oct. 20, 2014) The World Health Organization has declared Nigeria free of Ebola. Health experts credit a bit of luck and the government's initial response. Video provided by Newsy
Powered by NewsLook.com
How Detroit's Money Woes Led To U.N.-Condemned Water Cutoffs

How Detroit's Money Woes Led To U.N.-Condemned Water Cutoffs

Newsy (Oct. 20, 2014) The United Nations says water is a human right, but should it be free? Detroit has cut off water to residents who can't pay, and the U.N. isn't happy. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins