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New methods offer insight into regulatory DNA

Through the Human Genome Project, the HapMap Project and other efforts, we are beginning to identify genes that are modified in some diseases. More difficult to measure and identify are the regulatory regions in DNA ?the 'managers' of genes ?that control gene activity and might be important in causing disease.

Today, a team led by the Wellcome Trust Sanger Institute, together with colleagues in the USA and Switzerland, provide a measure of just how important regulatory region variation might be in a pilot study based on some 2% of the human genome. As many as 40 of 374 genes showed alteration in genetic activity that could be related to changes in DNA sequence called SNPs.

"We were amazed at the power of this study to detect associations between SNP variations and gene activity," commented Dr Manolis Dermitzakis, Investigator, Division of Informatics at the Wellcome Trust Sanger Institute. "We were even more amazed at the number of genes affected: more than 10% of our sample ?or perhaps 3000 genes across the genome ?could be subject to modification of activity in human populations due to common genetic variations."

The study combined the map of genetic variation developed through the HapMap with estimates of gene activity obtained from cell cultures from 60 individuals who provided samples for the HapMap. More than 630 genes were studied, of which 374 were active in the cell cultures. If gene activity in a cell culture was skewed from the average, it was investigated further.

These genes were correlated with more than 750,000 SNPs ?sequence differences between individuals in the sample collection. A series of statistical tests were carried out to provide increased confidence in the association between gene activity and sequence variation.

"Our sample size of 60 individuals is relatively small," continued Dr Dermitzakis, "and we might expect not to detect rare variations. However, our pilot project gives us greater confidence to
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Source:Public Library of Science


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