BioWorld International Correspondent

A German company and a British charity launched a project to examine DNA methylation across the human genome.

DNA methylation is a natural process that occurs mostly on cytosine bases and is a regulator of gene activity. While the process is needed for normal development, methylation changes have been detected with many cancers and some developmental disorders. Differences in the methylation pattern between healthy and diseased tissue can be detected and might indicate a change in gene activity that triggers disease.

The effort, dubbed the human epigenome project (HEP) is designed to identify and catalogue methylation variable positions (MVPs) in the human genome, eventually producing a map of methylation sites and linking gene sequence to regulation. Epigenomics AG, of Berlin, and the Wellcome Trust Sanger Institute in Cambridge, UK, will fund and carry out the first phase, in which they will identify and describe the sites in the human genome at which cytosine bases are modified by DNA methylation.

"This deal is a follow-up on a pilot project funded by the European Union," Kurt Berlin, chief scientific officer of Epigenomics, told BioWorld International. The pilot study examined methylation patterns within the major histocompatibility complex, a region on chromosome 6 that is associated with certain diseases. The partners determined the methylation status of more than 100,000 sites in the region.

"We expect the overall project to run roughly five years," Berlin said. "We think that we will be publishing the first dataset in mid- to late 2004." The public-private partnership is committed to releasing the sequence data as soon as possible. As a company, Epigenomics sees an opportunity to consolidate its intellectual property position in more specific applications of the project.

"We will be doing tissue-specific data on variation in methylation patterns," Berlin said, and those could be patented. "The company will patent part of the methylation for tissue type to disease correlations. One of our strategies is exclusive access to the methylation information that we discover."

Based on markers chosen through the process, Epigenomics will have additional means for driving its product development. "One function of the project is to strengthen awareness of how important methylation is," Berlin said. "There are very clear advantages compared with mRNA analysis - the DNA is stable, so it can be amplified and analyzed like you would do with SNPs."

Following the pilot study, for which the EU supplied €1.2 million in research funding, the existing partners committed funds, Berlin said.

"We expected to attract interest from other partners, and we are already in discussions about funding with both public and private sources," he said.

After the pilot project's examination of chromosome 6, the HEP will proceed through additional chromosomes.

"We'll be concentrating on the most interesting regions first, beginning with the best-annotated chromosomes such as number 22," Berlin said.

One reason that Berlin is optimistic about rapid progress is that the spots on the genome that could have methylation are not evenly distributed through the genome. First, it is a relatively rare base pair (approximately 1 in 70), and second, the pairs are concentrated in "CpG islands," portions of the genome with unusually high numbers of that pair. The combination of rarity and concentration should help the project partners apply their high-throughput sequencing and analysis approaches to the HEP.

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