Featured Research

from universities, journals, and other organizations

Importance Of Gene Regulation For Common Human Disease

Date:
September 19, 2007
Source:
Wellcome Trust Sanger Institute
Summary:
A new study shows that common, complex diseases are more likely to be due to genetic variation in regions that control activity of genes, rather than in the regions that specify the protein code. This surprising result comes from a study of the activity of almost 14,000 genes in 270 DNA samples collected for the HapMap Project.

A new study shows that common, complex diseases are more likely to be due to genetic variation in regions that control activity of genes, rather than in the regions that specify the protein code.

This surprising result comes from a study at the Wellcome Trust Sanger Institute of the activity of almost 14,000 genes in 270 DNA samples collected for the HapMap Project. The authors looked at 2.2 million DNA sequence variants (SNPs) to determine which affected gene activity.

They found that activity of more than 1300 genes was affected by DNA sequence changes in regions predicted to be involved in regulating gene activity, which often lie close to, but outside, the protein-coding regions.

"We predict that variants in regulatory regions make a greater contribution to complex disease than do variants that affect protein sequence," explained Dr Manolis Dermitzakis, senior author from the Wellcome Trust Sanger Institute. "This is the first study on this scale and these results are confirming our intuition about the nature of natural variation in complex traits.

"One of the challenges of large-scale studies that link a DNA variant to a disease is to determine how the variant causes the disease: our analysis will help to develop that understanding, a vital step on the path from genetics to improvements in healthcare."

Past studies of rare, monogenic disease, such as cystic fibrosis and sickle-cell anaemia, have focused on changes to the protein-coding regions of genes because they have been visible to the tools of human genetics. With the HapMap and large-scale research methods, researchers can inspect the role of regions that regulate activity of many thousands of genes.

The HapMap Project established cell cultures from participants from four populations as well as, for some samples, information from families, which can help to understand inheritance of genetic variation. The team used these resources to study gene activity in the cell cultures and tie that to DNA sequence variation

'We have generated an information resource readily available to investigators working in the mapping of variants underlying complex traits. Regions of association can be correlated with signatures of regulatory regions affecting gene expression' explained Dr Panos Deloukas, Senior Investigator at the Wellcome Trust Sanger Institute

"We found strong evidence that SNP variation close to genes - where most regulatory regions lie - could have a dramatic effect on gene activity," said Dr Barbara Stranger, post-doctoral fellow at WT Sanger Institute. "Although many effects were shared among all four HapMap populations, we have also shown that a significant number were restricted to one population."

They also showed that genes required for the basic functions of the cell - so-called housekeeping genes - were less likely to be subject to genetic variation. "This was exactly as we would expect: you can't mess too much with the fundamental life processes and we predicted we would find reduced effects on these genes," said Dr Dermitzakis.

The study also detected SNP variants that affect the activity of genes located a great distance away. Genetic regulation in the human genome is complex and highly variable: a tool to detect such distant effects will expand the search for causative variants. The authors note, however, that the small sample size of 270 HapMap individuals is sensitive enough to detect only the strongest effects.

The results of this study are becoming available in public databases such as Ensembl for researchers to use.

Reference: Stranger BE et al. (2007) Population genomics of human gene expression. Nature Genetics advance online publication, 16 September, 2007

The paper is accompanied by two others examining effects of changes to regulatory DNA in samples from asthma and from heart study patients.

Funding was provided by the Wellcome Trust, the US National Institutes of Health ENDGAME, Cancer Research UK and the Medical Research Council.


Story Source:

The above story is based on materials provided by Wellcome Trust Sanger Institute. Note: Materials may be edited for content and length.


Cite This Page:

Wellcome Trust Sanger Institute. "Importance Of Gene Regulation For Common Human Disease." ScienceDaily. ScienceDaily, 19 September 2007. <www.sciencedaily.com/releases/2007/09/070916143515.htm>.
Wellcome Trust Sanger Institute. (2007, September 19). Importance Of Gene Regulation For Common Human Disease. ScienceDaily. Retrieved April 18, 2014 from www.sciencedaily.com/releases/2007/09/070916143515.htm
Wellcome Trust Sanger Institute. "Importance Of Gene Regulation For Common Human Disease." ScienceDaily. www.sciencedaily.com/releases/2007/09/070916143515.htm (accessed April 18, 2014).

Share This



More Health & Medicine News

Friday, April 18, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Scientists Create Stem Cells From Adult Skin Cells

Scientists Create Stem Cells From Adult Skin Cells

Newsy (Apr. 17, 2014) The breakthrough could mean a cure for some serious diseases and even the possibility of human cloning, but it's all still a way off. Video provided by Newsy
Powered by NewsLook.com
Obama: 8 Million Healthcare Signups

Obama: 8 Million Healthcare Signups

AP (Apr. 17, 2014) President Barack Obama gave a briefing Thursday announcing 8 million people have signed up under the Affordable Care Act. He blasted continued Republican efforts to repeal the law. (April 17) Video provided by AP
Powered by NewsLook.com
Is Apathy A Sign Of A Shrinking Brain?

Is Apathy A Sign Of A Shrinking Brain?

Newsy (Apr. 17, 2014) A recent study links apathetic feelings to a smaller brain. Researchers say the results indicate a need for apathy screening for at-risk seniors. Video provided by Newsy
Powered by NewsLook.com
Could Even Casual Marijuana Use Alter Your Brain?

Could Even Casual Marijuana Use Alter Your Brain?

Newsy (Apr. 16, 2014) A new study conducted by researchers at Northwestern and Harvard suggests even casual marijuana use can alter your brain. 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:
from the past week

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