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Current DNA Chips Ill-Equipped to Handle Multiple mRNA Transcripts

This article has been updated to include the author's comment.


NEW YORK, June 14 - More than half of all human genes encode multiple mRNA transcripts that end in different locations, a finding that suggests that currently available microarrays may not be up to snuff to handle the extra data, according to recent research.


Scientists today know that the ends of mRNA transcripts contain relatively short variations, which are not generally accounted for when preparing DNA probes. But research from the Ludwig Institute for Cancer Research in Lausanne, Switzerland, claims that these variations are spread over a much larger distance--1,000 nucleotides--and are driven by multiple genomic signals.


As a result, current DNA chips will find it difficult to "capture the full complexity" of mRNA, according to the study authors.


"These findings have profound implications for understanding how genes function," said Victor Jongeneel, a study leader and director of the Ludwig institute's office of information technology. "We need better DNA chips to match the increasing complexity of our genes."


His team's work will be published in the July issue of Genome Research.


Working in collaboration with the National Cancer Institute, Jongeneel's team reviewed public data on the human genome and its transcriptome. Specifically, the scientists looked at the part of the mRNA located ahead of the poly (A) tails. Analyzing a portion of chromosome 21, the team saw that "long-range variations" in these mRNA tails "affect at least half of the genes" found on the chromosome. They speculate that these variations exist in about 20,000 of the 35,000 estimated human genes.


"Including more mRNA tags for analysis should boost the amount of information that can be gathered in each experiment, and thus open new avenues for the diagnostic use of DNA chips," Jongeneel said.


In an e-mail message, Jongeneel, who is at a meeting in China this week, said he has no plans to develop or commercialize microarrays "that take into account our new data."


But he said his lab has "started a collaboration" with Zeptosens, a Swiss microarray company owned by Qiagen, "to assess the impact that our data would have on the informativity of microarray results obtained from cancer samples."

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