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Individual differences caused by shuffled chunks of DNA in the human genome
Date:9/27/2007

enome DNA into manageable-sized pieces about 3000 bases long; tagged and rescued the paired ends of the fragments; and then analyzed their sequence with a high-throughput, rapid-sequencing method developed by 454 Life Sciences.

454 Sequencing can generate hundreds of thousands of long read pairs that are unique within the human genome to quickly and accurately determine genomic variations, explained Michael Egholm, a co-author of the study and vice president of research and development at 454 Life Sciences.

Previous work, based on point mutations estimated that there is a 0.1 percent difference between individuals, while this work points to a level of variation between two- and five-times higher, said Snyder.

We also found hot spots particular regions where there is a lot of variation, said Korbel. While these regions may be still actively undergoing evolution, they are often regions associated with genetic disorder and disease.

These results will have an impact on how people study genetic effects in disease, said Alex Eckehart Urban, a graduate student in Snyders group, and one of the principal authors on the study. It was previously assumed that landmarks, like the SNPs mentioned earlier, were fairly evenly spread out in the genomes of different people. Now, when we are hunting for a disease gene, we have to take into account that structural variations can distort the map and differ between individual patients.

While it may sound like a contradiction, says Snyder, this study supports results we have previously reported about gene regulation as the primary cause of variation. Structural variation of large of spans of the genome will likely alter the regulation of individual genes within those sequences.

According to the authors, even in healthy people, there are variants in which part of a gene is deleted or sequences from two genes are fused together with
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Contact: Janet Rettig Emanuel
janet.emanuel@yale.edu
203-432-2157
Yale University
Source:Eurekalert

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