Featured Research

from universities, journals, and other organizations

'Gene desert' on chromosome 9 is hotspot for coronary artery disease risk

Date:
February 10, 2011
Source:
University of California - San Diego
Summary:
The discovery that a "gene desert" on chromosome 9 was a hotspot for coronary artery disease risk was among the highlights of findings produced recently by genome-wide association studies, which compare the genomes of many people for genetic variations and have been broadly used in the past few years to study hundreds of diseases and complex traits. Gene deserts are large genomic segments devoid of genes. Now scientists have developed a novel approach to detect long-distance chromosomal interactions and have applied this method to the chromosome 9 gene desert, revealing that the association results from an altered inflammatory signaling response in individuals with increased CAD risk.

The discovery that a "gene desert" on chromosome 9 was a hotspot for coronary artery disease (CAD) risk was among the highlights of findings produced recently by genome-wide association studies, which compare the genomes of many people for genetic variations and have been broadly used in the past few years to study hundreds of diseases and complex traits. Gene deserts are large genomic segments devoid of genes.

Related Articles


Now scientists at the University of California, San Diego School of Medicine and colleagues have developed a novel approach to detect long-distance chromosomal interactions and have applied this method to the chromosome 9 gene desert, revealing that the association results from an altered inflammatory signaling response in individuals with increased CAD risk.

The findings are published in the Feb. 10 issue of Nature.

The researchers followed up on results of the widely reported genome-wide association studies in 2007 and 2008, noting that the gene desert interval on chromosome 9 contained DNA variants (called single nucleotide polymorphisms or SNPs) associated with CAD and type 2 diabetes mellitus (T2D).

The DNA variants associated with CAD and T2D are located close to one another on chromosome 9, but inherited independently so genetic risk for developing CAD is not associated with risk for the T2D.

In comparing the genomes of people with heart disease and people without, Frazer and colleagues found that those who carried the chromosome 9 DNA risk variants for CAD had a two-fold higher risk of early onset myocardial infarction (a heart attack) than non-carriers.

"The association of this interval with CAD was a surprise and not expected as it is a 'gene desert' and the flanking genes, which are far away, have little to do with lipid metabolism, one of the primary factors in heart disease," said one of the study's corresponding authors Kelly A. Frazer, PhD, professor in the Moores Cancer Center, UCSD Department of Pediatrics and Rady Children's Hospital San Diego, a research and teaching affiliate of the UCSD School of Medicine.

The research team took an even closer look at the relevant region of chromosome 9, called 9p21, and discovered that the 9p21 DNA sequence, which is devoid of protein-coding genes, is particularly rich in potential regulatory elements influencing disease risk. They identified 33 "enhancers" or regulatory elements responsible for activating or repressing genes. The researchers determined that the 9p21 interval is the second densest interval for predicted enhancers in the entire human genome, and six times denser than the genome on average.

The DNA variants associated with CAD appear to disrupt enhancer activity involved in cellular signaling and response to inflammation in vascular endothelial cells -- the cells that form the inner lining of major blood vessels.

"Our work highlights the new approach we developed for analyzing long-range chromosomal interactions and the utility of such methods for deciphering the functions of non-coding DNA variants associated with disease risk," said Michael G. Rosenfeld, MD, a professor in the UCSD Department of Medicine, Howard Hughes Medical Institute investigator and a corresponding author of the study.

The UCSD researchers plan to scale up the new approach and use other methods to annotate additional non-coding DNA variants identified through GWAS studies as being linked to human disease.

"There are thousands of DNA regulatory variants that incur increased risk for disease that we can functionally characterize for their effect on long-range interactions," said Olivier Harismendy, PhD, first author of the study and an assistant project scientist in the UCSD Department of Pediatrics and Moores Cancer Center.

Co-authors of the study include Dimple Notani, Xiaoyuan Song and Bogdan Tanasa of the UCSD Department of Medicine, Howard Hughes Medical Institute; Xiang-Dong Fu of the UCSD Department of Cellular and Molecular Medicine; Nathaniel Heintzman and Bing Ren of the Ludwig Institute for Cancer Research; and Nazli G. Rahim and Eric J. Topol of Scripps Genomic Medicine, Scripps Translational Science Institute and The Scripps Research Institute.

Based on these findings, Francis Collins, director of the National Institutes of Health and a leader in the original Human Genome Project, publicly described the chromosome 9 interval as "like the seat of the soul of the genome."


Story Source:

The above story is based on materials provided by University of California - San Diego. Note: Materials may be edited for content and length.


Journal Reference:

  1. Olivier Harismendy, Dimple Notani, Xiaoyuan Song, Nazli G. Rahim, Bogdan Tanasa, Nathaniel Heintzman, Bing Ren, Xiang-Dong Fu, Eric J. Topol, Michael G. Rosenfeld, Kelly A. Frazer. 9p21 DNA variants associated with coronary artery disease impair interferon-γ signalling response. Nature, 2011; 470 (7333): 264 DOI: 10.1038/nature09753

Cite This Page:

University of California - San Diego. "'Gene desert' on chromosome 9 is hotspot for coronary artery disease risk." ScienceDaily. ScienceDaily, 10 February 2011. <www.sciencedaily.com/releases/2011/02/110209131822.htm>.
University of California - San Diego. (2011, February 10). 'Gene desert' on chromosome 9 is hotspot for coronary artery disease risk. ScienceDaily. Retrieved October 31, 2014 from www.sciencedaily.com/releases/2011/02/110209131822.htm
University of California - San Diego. "'Gene desert' on chromosome 9 is hotspot for coronary artery disease risk." ScienceDaily. www.sciencedaily.com/releases/2011/02/110209131822.htm (accessed October 31, 2014).

Share This



More Health & Medicine News

Friday, October 31, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Melafind: Spotting Melanoma Without a Biopsy

Melafind: Spotting Melanoma Without a Biopsy

Ivanhoe (Oct. 31, 2014) The MelaFind device is a pain-free way to check suspicious moles for melanoma, without the need for a biopsy. Video provided by Ivanhoe
Powered by NewsLook.com
Battling Multiple Myeloma

Battling Multiple Myeloma

Ivanhoe (Oct. 31, 2014) The answer isn’t always found in new drugs – repurposing an ‘old’ drug that could mean better multiple myeloma treatment, and hope. Video provided by Ivanhoe
Powered by NewsLook.com
Chronic Inflammation and Prostate Cancer

Chronic Inflammation and Prostate Cancer

Ivanhoe (Oct. 31, 2014) New information that is linking chronic inflammation in the prostate and prostate cancer, which may help doctors and patients prevent cancer in the future. Video provided by Ivanhoe
Powered by NewsLook.com
Sickle Cell: Stopping Kids’ Silent Strokes

Sickle Cell: Stopping Kids’ Silent Strokes

Ivanhoe (Oct. 31, 2014) Blood transfusions are proving crucial to young sickle cell patients by helping prevent strokes, even when there is no outward sign of brain injury. Video provided by Ivanhoe
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