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Prostate cancer risk variant found to be in a functional DNA sequence linked with disease
Date:7/12/2010

July 13, 2010 Recent genetic association studies have uncovered a number of DNA variants associated with prostate cancer. However, some of these risk variants lie outside of genes, posing a challenge to researchers working to understand the biology of cancer. In a report published online today in Genome Research (http://www.genome.org), researchers have characterized a functional DNA element associated with prostate cancer, lending new insight into the molecular mechanisms of the disease.

Genome wide association studies (GWAS) have uncovered numerous genetic variants that confer increased risk to disease, and interestingly, many reside in genomic regions that lack genes. Although the DNA may not code for a gene, it could still play a functional role. "This raises the question of what non-coding DNA within these gene deserts actually has biological function, and how differences within a functional non-coding element could underlie disease risk," said Marcelo Nobrega of the University of Chicago, senior author of the study.

Recent GWAS have implicated a specific region of chromosome 8, known as 8q24, for harboring non-coding risk variants for several different cancers, including particularly strong associations with prostate cancer. Variants in this region could lie within enhancer elements, non-coding DNA sequences that control how, when, and where genes are expressed. An altered enhancer sequence could significantly change the normal expression of critical genes, increasing risk for disease.

To test this hypothesis, the group designed an experiment to investigate the enhancer activity of human 8q24 DNA fragments and whether risk alleles of the enhancer modify that activity. The group engineered DNA segments that included the human sequences and a "reporter" gene that would indicate whether any enhancers are present in the human DNA.

They then created transgenic mice that harb
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Contact: Peggy Calicchia
calicchi@cshl.edu
516-422-4012
Cold Spring Harbor Laboratory
Source:Eurekalert

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