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Researchers unlock disease information hidden in genome's control circuitry
Date:9/5/2012

that turn genes on and off. In many cases, these switches are located far away from the genes that they control. These distances have made it difficult to determine the relationship between specific switches and genes.

The researchers used a special molecular probe called a nuclease to detect all of the regulatory regions active in each cell type they studied. The specific nuclease they used -- called DNase I -- snips the genome where regulatory factors are bound to DNA. By treating cells with DNase I and analyzing the pattern of snipped DNA sequences using massively parallel sequencing technology and high-performance computers, the researchers were able to create comprehensive maps of all the regulatory DNA in many different types of cells. These maps were then analyzed with advanced software algorithms to sort through the data and expose previously hidden connections between disease-associated genetic variation and specific regulatory regions.

The regulatory mapping and analysis was conducted on 349 cell and tissue samples. These included samples from all major organs as well as 233 tissue samples from different stages of early human development. In total, nearly 4 million distinct regulatory regions were discovered, though only about 200,000 of these were 'on' in any particular cell type.

To make a connection with common diseases and clinical traits, the researchers analyzed genetic variants that had been strongly associated with diseases and traits through so-called genome-wide association studies, which compare genetic information between groups of people with or without a particular disease or trait. During the past decade, hundreds of genome-wide association studies involving hundreds of thousands of patients worldwide have been performed for over 400 diseases and traits. Nearly 95 percent of the time, these studies flagged genetic variants that were located outside of gene protein-coding regions. Comparison of these da
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Contact: Leila Gray
leilag@uw.edu
206-543-3620
University of Washington
Source:Eurekalert  

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