Navigation Links
Diseases of aging map to a few 'hotspots' on the human genome
Date:9/19/2012

Researchers have long known that individual diseases are associated with genes in specific locations of the genome. Genetics researchers at the University of North Carolina at Chapel Hill now have shown definitively that a small number of places in the human genome are associated with a large number and variety of diseases. In particular, several diseases of aging are associated with a locus which is more famous for its role in preventing cancer.

For this analysis, researchers at UNC Lineberger Comprehensive Cancer Center catalogued results from several hundred human Genome-Wide Association Studies (GWAS) from the National Human Genome Research Institute. These results provided an unbiased means to determine if varied different diseases mapped to common 'hotspot' regions of the human genome. This analysis showed that two different genomic locations are associated with two major subcategories of human disease.

"Our team is interested in understanding genetic susceptibility to diseases associated with aging, including cancer," said PhD student William Jeck, who was first author on the study, published in the journal Aging Cell.

The team examined the large NHGRI dataset and first eliminated hereditable traits such as eye or hair color and other non-disease traits like drug metabolism. The group then focused on variants identified from GWAS that contributed to actual diseases. Combining results from all of these studies, there was enough data to arrive at statistically valid conclusions. The team then mapped the disease associations to the appropriate locations of the genome, counting the number of unique diseases mapping to specific genomic regions, in order to see if disparate diseases mapped randomly throughout the genome, or clustered in hotspots.

"What we ended up with is a very interesting distribution of disease risk across the genome. More than 90 percent of the genome lacked any disease loci. Surprisingly, however, lots of diseases mapped to two specific loci, which soared above all of the others in terms of multi-disease risk. The first locus at chromosome 6p21, is where the major histocompatibility (MHC) locus resides. The MHC is critical for tissue typing for organ and bone marrow transplantation, and was known to be an important disease risk locus before genome-wide studies were available. Genes at this locus determine susceptibility to a wide variety of autoimmune diseases such as arthritis, celiac disease, Type I diabetes, asthma, psoriasis, and lupus," said Jeck.

"The second place where disease associations clustered is the INK4/ARF (or CDKN2a) tumor suppressor locus. This area, in particular, was the location for diseases associated with aging: atherosclerosis, heart attacks, stroke, Type II diabetes, glaucoma and various cancers." he added.

"The finding that INK4/ARF is associated with lots of cancer, and MHC is associated with lots of diseases of immunity is not surprisingthese associations were known. What is surprising is the diversity of diseases mapping to just two small places: 30 percent of all tested human diseases mapped to one of these two places. This means that genotypes at these loci determine a substantial fraction of a person's resistance or susceptibility to multiple independent diseases," said Ned Sharpless, MD, Wellcome Distinguished Professor of Cancer Research and Associate Director of Translational Research at UNC Lineberger.

Another interesting finding was the apparent role of two biological processes in multi-disease association. In addition to the MHC and INK4/ARF loci, five less significant hotspot loci were also identified. Of the seven total hotspot loci, however, all contained genes associated with either immunity or cellular senescence. Cellular senescence is a permanent form of cellular growth arrest, and it is an important means whereby normal cells are prevented from becoming cancerous. It has been long known that senescent cells accumulate with aging, and may cause aspects of aging. This new analysis provides evidence that genetic differences in an individual's ability to regulate the immune response and activate cellular senescence determine their susceptibility to many seemingly disparate diseases.

"We call the absence of disease 'wellness', and our results suggest the genetics of wellness may be much more simple than previously suspected. Put another way, these unbiased data from about two million people suggest that your eccentric Uncle Joe, who drank and smoked, but who also lived to be 110 and was never sick a day in his lifewell Uncle Joe may have just been genetically fortunate at a couple of loci," said Sharpless.


'/>"/>

Contact: Ellen de Graffenreid
edegraff@med.unc.edu
919-962-3405
University of North Carolina Health Care
Source:Eurekalert

Related medicine news :

1. First Pathfinder Awards announced tackling rare and orphan diseases
2. Leading stem cell scientists to focus on diabetes, eye diseases at Cedars-Sinai symposium
3. Study suggests gap in treatment of sexually transmitted diseases among teens
4. New grant awards aim to prevent autoimmune diseases
5. Funding for neglected global diseases research at UBC exceeds $20 million
6. Scientists Inch Closer to Genetic Blueprint of Diseases
7. Can gene therapy cure fatal diseases in children?
8. Human Airways Brush Mechanism Gives Clues to Lung Diseases
9. New insights into why humans are more susceptible to cancer and other diseases
10. Rejected drug may protect against toxic substance common to Alzheimers and Parkinsons diseases
11. Pioneering research into rare neonatal diseases
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/26/2016)... San Rafael, CA (PRWEB) , ... May 26, ... ... Studio will be offering campers a multitude of activities from daily practices, arts ... and self-confidence. , Camp Directors Amber East-D’Anna and Christy Evans have combined backgrounds ...
(Date:5/26/2016)... ... ... The MIAMI Institute for Age Management and Intervention celebrates Global Wellness Day with ... Adonis , Wellness Physician of the MIAMI Institute is certified by the American Academy ... , He also heads up FITTLab, the comprehensive medical testing lab located in The ...
(Date:5/26/2016)... ... 26, 2016 , ... Power Systems, a leading developer and ... Certification Course in Stoughton, Massachusetts. The course was led by Power Systems’ Education ... hour interactive course to qualify participants as certified PowerWave trainers. , PowerWave ...
(Date:5/26/2016)... (PRWEB) , ... May 26, 2016 , ... ... information to oncology professionals, has added National Cancer Institute-designated University of Virginia ... , In this new partnership, OncLive’s editorial and marketing teams will publicize and ...
(Date:5/26/2016)... City, CA (PRWEB) , ... May 26, 2016 , ... ... Silicon Valley-based startup, The Dough Bar, has ignited an undeniable buzz in ... -- a doughnut. But not just any doughnut.  These doughnuts are packed with 11 ...
Breaking Medicine News(10 mins):
(Date:5/26/2016)... WASHINGTON , May 26, 2016 ... Microspheres, Associated With Both Cost Savings and ... BTG plc (LSE: BTG), an international specialist healthcare ... data at the 21st Annual Meeting of ISPOR ... that treatment of hepatocellular carcinoma (HCC) using yttrium-90 ...
(Date:5/26/2016)... , May 26, 2016 Since ... matured into an essential life science tool for conducting ... applications. BCC Research reveals in its new report that ... growth phase, one powered by a range of new ...      (Logo: http://photos.prnewswire.com/prnh/20140723/694805 ) , ...
(Date:5/25/2016)... 25, 2016 According to a ... (3D, 2D, 4D), by Therapeutic Area (Oncology, Cosmeceutical/Plastic Surgery), ... (Medical Device Manufacturers, Hospitals/ Clinics) - Forecast to 2021", ... Animation Market for the forecast period of 2016 to ... Million by 2021 from USD 117.3 Million in 2016, ...
Breaking Medicine Technology: